Research for Better Treatment of Childhood Cancer

The Cancer Evolution and Genomics research group at ST. Anna CCRI, led by George Cresswell, investigates how childhood cancer develops and why some patients respond differently to treatments. The scientists analyze how genetic changes evolve in tumors and aim to identify new approaches for better treatments. The goal: to detect cancer earlier, treat it more precisely, and improve long-term survival chances.

Why Do Children Respond Differently to Cancer Therapies?

Every tumor is unique and changes over time. Some cancer cells develop mechanisms to evade therapy. This means that a treatment that is successful for one child may not work for another. The research group focuses on investigating these genetic changes in detail. By understanding which mutations (changes in genetic material) are responsible, treatments can be tailored more precisely, and potentially new therapies can be developed.

Current Research Projects

1. How Does a Dangerous Kidney Tumor Change at the Cellular Level?

One research focus is high-risk Wilms tumor, a particularly aggressive form of childhood kidney cancer. These tumors are often characterized by a mutation in the TP53 gene, making them especially difficult to treat. It is known that these tumors exhibit numerous chromosomal changes, but how this manifests as chromosomal instability has not been fully resolved.

The team is now analyzing different Wilms tumor models to determine the extent of this instability. These findings could explain why this tumor often responds poorly to therapies. In the long term, this knowledge may help develop better treatment strategies.

2. New Insights into a Dangerous Nerve Tumor

Another project focuses on neuroblastoma, a tumor of the nervous system that is often fatal. About half of affected children fall into the high-risk group, where survival rates are currently only around 50%.

Many aggressive neuroblastomas show characteristic genetic changes, especially in chromosomes. A large international study is collecting and analyzing data from around 1,500 affected children in Europe. The goal is to identify patterns associated with particularly poor disease outcomes.

With the help of artificial intelligence (machine learning), researchers aim to determine which genetic characteristics indicate a poor prognosis. These insights could enable the development of more targeted and effective treatments in the future.

3. Blood Tests as an Alternative to Biopsies – Cancer Monitoring Without Surgery?

Tumor tissue sampling is often stressful for patients, requiring either surgery or a needle biopsy. However, a promising new method is emerging: liquid biopsy. Instead of directly examining the tumor, this approach analyzes small traces of tumor DNA circulating in the blood. This method offers several advantages:

  • No invasive procedure: A simple blood sample replaces surgery or needle biopsies.
  • Better tumor overview: Tumors often consist of different cell types that are not evenly distributed in the tissue. A tissue biopsy may provide incomplete information, whereas a blood sample contains DNA traces from various parts of the tumor, offering a more comprehensive picture.
  • Early detection of relapses: Cancer can return after successful treatment. A liquid biopsy could detect cancer recurrence earlier, even before it appears on conventional scans.

The team is testing whether this method is reliable for children with different solid tumors. Using special DNA analyses, researchers are searching for typical genetic changes in patients’ blood samples. If successful, this method could revolutionize cancer diagnostics, allowing disease monitoring and treatment adjustments without repeated surgeries or invasive procedures.

4. New Methods for Tumor Analysis

Understanding cancer requires more precise analytical methods. A visiting scientist in the group is developing a new technique for analyzing tumor DNA, focusing on genetic alterations, including mutations and epigenetic patterns (chemical changes in DNA that influence gene behavior).

This technique uses a special statistical method designed to produce particularly reliable results. If successful, it could improve both cancer research and clinical diagnostics, enabling faster and more precise tumor classification and helping to select the best individualized therapy for each child.

Goal: Better Treatments for Children with Cancer

The Cancer Evolution and Genomics research group’s work contributes to a better understanding of childhood cancer and the development of new diagnostic and therapeutic methods. Particularly exciting are the liquid biopsy and artificial intelligence approaches, which could revolutionize treatment options in the long run.

The overarching goal is to enable personalized cancer therapy—treatments tailored precisely to the genetic characteristics of the tumor. This approach could not only improve survival rates but also reduce side effects. Every new discovery brings us closer to this goal.

Networking as a natural consequence of outstanding research …with Florian Halbritter

In modern science, collaboration is the key to innovation and breakthroughs, especially in complex research fields such as cancer genomics. Florian Halbritter, head of the “Developmental Cancer Genomics” research group at St. Anna Children’s Cancer Research Institute, exemplifies the importance of this interdisciplinary collaboration with his work.

As a bioinformatician, Florian Halbritter and his team work at the interface between biology, medicine, statistics and computer science. The close collaboration between the disciplines is now deeply rooted in his research approach. To get there, he has gathered many different impressions along the way and has often felt like an “oddball” in new fields of research: as a computer scientist among stem cell researchers, as a stem cell researcher among epigeneticists and immunologists and now as an epigeneticist among cancer researchers. “I have learned to feel comfortable in this role and try to approach new topics with curiosity and humility,” he says in the interview.

Halbritter has reassuring words for young researchers who feel insecure when it comes to building their own network: he does not see networking in science as a dedicated task, but as something that arises naturally through outstanding work. What he particularly appreciates about St. Anna CCRI is the close cooperation between the groups, which often results in joint international projects and thus promotes the exchange of knowledge and expertise on a global level.

To what extent do interdisciplinary collaboration and knowledge exchange play a role in your research?

Interdisciplinarity is essentially built into our approach. As bioinformaticians, we operate at the interface of biology, medicine, statistics, and computer science. My colleagues and collaboration partners hail from these diverse fields, and our daily exchange fosters fresh perspectives and makes research even more exciting.

How has the importance of collaboration changed due to technological advances?

Thanks to technological breakthroughs, we can now conduct a multitude of biomolecular measurements on the same samples while simultaneously analyzing many samples at once. Handling all these technologies and analyzing the resulting datasets is rarely manageable by a single individual. Collaboration has therefore become even more crucial.

What specific projects or research topics connect you and your research group with other groups within the CCRI?

We collaborate with nearly all groups at the CCRI on one or another project. Our primary focus lies on the early developmental stages of pediatric cancer. In order to explore and model these stages, we combine our analytical approaches with the expertise of specialists in various types of pediatric cancer at the CCRI. For instance, we work in a big project on Ewing sarcoma together with Heinrich Kovar and Martin Distel – this is funded by American charity Alex’s Lemonade Stand Foundation –, or together with Sabine Taschner-Mandl on neuroblastoma.

What do you value about working with the other groups?

Throughout my career, I’ve always found myself as a kind of oddball and newcomer: as a computer scientist among stem cell researchers, as a stem cell researcher among epigeneticists and immunologists, and now as an epigeneticist among cancer researchers. I have learnt to be comfortable in this role and try to approach new topics with curiosity and humility. I couldn’t do this on my own. Working with other research groups, who are experts in completely different fields, allows us to efficiently dive into these new topics and to make new discoveries together.

What are your tips for young researchers who are just starting to build a network? Are there opportunities to network at CCRI?

I wouldn’t necessarily think of networking as a task or requirement that needs to be accomplished. Simply remain receptive to the insights and contributions of others while offering your own assistance whenever possible. Good work organically fosters the growth of your network. At CCRI, collaboration and exchange among groups are pervasive, often extending to international projects, which presents numerous avenues for engagement.

How would you assess the importance of international collaborations for the success of your research group?

International collaborations not only facilitate broad knowledge exchange but also pool resources and expertise in new technologies. This makes it possible to tackle even more complex research questions and to extend the scope of our investigations. Additionally, these collaborations enhance the visibility of our work on a global scale and foster long-term partnerships that help to advance scientific breakthroughs.

Which other national or international research institutes, industrial partners or companies do you work with as part of your research activities? Which projects and how?

We often engage in collaborations with researchers in other institutions both in Austria and elsewhere in the world. For instance, we work with the genomics facilities at CeMM and the Vienna Biocenter to access their state-of-the-art technologies or with clinician-scientists and pathologists at the Medical University of Vienna to analyze tumor tissues. Internationally, we leverage a network of stem cell and developmental biologists in our efforts to model different types of pediatric cancers. For example, we are just about to start a new project on Wilms tumor in which we will work with the RIKEN institute in Japan. 

A Light Against Cancer

A team of scientists at St. Anna Children’s Cancer Research Institute (St. Anna CCRI) has developed a method to eliminate cancer cells with precision, without harming healthy tissue. Using a light-activatable compound called SBTubA4P, they successfully destroyed tumor cells in an animal model. This promising discovery could one day offer a gentler alternative to chemotherapy.

Traditional chemotherapy relies on highly potent drugs that kill cancer cells. However, these medications also attack healthy cells, often causing severe side effects. Researchers are therefore searching for alternatives that exclusively target tumor cells. One promising approach is photopharmacology, in which drugs are activated only by targeted light exposure.

First author, PhD-Student Adam Varady and a research team at St. Anna Children’s Cancer Research Institute (St. Anna CCRI) focused on SBTubA4P, a chemical compound that remains harmless in its inactive state. Only when exposed to ultraviolet (UV) light does the drug activate and unleash its cancer-fighting effects. The key advantage: Activation can be precisely directed at the tumor, leaving healthy tissue untouched.

Larval zebrafish sarcoma xenograft
zebrafish larva with transplanted sarcoma cells (green), metastases can be seen in the tail

A Model for Human Cancer

To test the effectiveness of this method, the researchers used a specialized zebrafish model. The larvae of these fish are transparent, allowing direct observation of cancer cells. The scientists implanted human bone cancer cells (osteosarcoma and Ewing sarcoma) into the fish and treated them with SBTubA4P. The tumor was then specifically exposed to UV light.

The results were remarkable: The cancer cells died while the surrounding tissue remained intact. In some cases, tumors disappeared entirely without causing systemic side effects.

The researchers also discovered an additional mechanism that enhances SBTubA4P’s effectiveness. Under UV exposure, the molecule generates reactive oxygen species (ROS). These aggressive molecules damage the structures of cancer cells, accelerating their destruction.

Potential Applications in Medicine

Although this method, published in the journal Disease Models & Mechanisms, has so far only been tested in zebrafish, it could one day be applied to humans. One challenge remains: the delivery of light. UV light penetrates only a few millimeters into tissue. Possible solutions could include optical fibers that direct light precisely into the tumor or novel materials that transfer high-energy light to the drug.

“Our study shows that SBTubA4P is a promising candidate for precise cancer therapy,” explains lead researcher Martin Distel. “The next step is to further develop this approach to make it suitable for clinical applications.”

Light-controlled chemotherapy using SBTubA4P could one day offer a more targeted and less harmful treatment option for cancer patients. The research is still in its early stages, but the results provide a hopeful outlook for a new generation of precise cancer therapies.

Natural Killer Cells in the Fight Against Neuroblastoma

A recently published review in Cancer and Metastasis Reviews highlights promising therapeutic strategies utilizing natural killer (NK) cells to combat neuroblastoma, an aggressive pediatric tumor of the sympathetic nervous system. Researchers from St. Anna Children’s Cancer Research Institute and the Medical University of Vienna emphasize that NK cells play a crucial role in the tumor microenvironment and hold significant potential for innovative treatment strategies.

Natural killer (NK) cells are vital components of the innate immune system, capable of detecting and eliminating stressed or transformed cells without prior sensitization. Unlike T-cell-based therapies, NK-cell therapies do not require personalized approaches since NK cells lack T-cell receptors. “This opens the door for so-called ‘off-the-shelf’ immunotherapies, which can be made available more quickly and cost-effectively,” explains Sabine Taschner-Mandl, Principal Investigator at St. Anna Children’s Cancer Research Institute.

Challenges in Neuroblastoma Treatment

Neuroblastoma is among the deadliest solid tumors in children, particularly in high-risk groups, where mortality rates exceed 50%. While NK-cell immunotherapies have been successful in treating blood cancers, they face considerable challenges in solid tumors like neuroblastoma. The tumor microenvironment (TME) plays a key role in modulating immune responses, often suppressing effective immune attacks.

The TME in neuroblastoma is poorly immunogenic, characterized by low infiltration of T and NK cells. This reduced immunogenicity is partially due to the tumor’s low mutation burden. “Low-risk neuroblastomas show increased infiltration of T and NK cells, correlating with better clinical outcomes,” says Irfete Fetahu from the Medical University of Vienna. However, in high-risk neuroblastomas, immune checkpoint molecules, stromal, and myeloid cells contribute to immune suppression.

Innovative Therapeutic Approaches and Advances

Despite these challenges, significant advancements have been made. One of the leading immunotherapeutic strategies for neuroblastoma involves antibodies targeting the tumor-associated disialoganglioside GD2. NK cells can recognize the Fc fragments of these antibodies and eliminate tumor cells via antibody-dependent cellular cytotoxicity (ADCC). Clinical trials with the anti-GD2 antibody dinutuximab have shown substantial improvements in survival rates for neuroblastoma patients and have become standard treatment.

Another breakthrough is the development of genetically engineered NK cells equipped with chimeric antigen receptors (CAR). These CAR-NK cells are designed to better recognize and target tumor-specific receptors. “CAR-NK cells have the potential to be safer and more effective than CAR-T cells, as they persist in the body for a shorter duration and cause fewer side effects,” notes Magdalena Rados from St. Anna Children’s Cancer Research Institute.

However, a major hurdle remains the limited immune surveillance by NK cells. Tumor cells often develop mechanisms to evade immune detection, such as downregulating MHC class I molecules, which NK cells typically recognize. Researchers are actively exploring strategies to enhance NK-cell function in the tumor microenvironment and overcome these immunosuppressive mechanisms.

A particularly promising approach is the combination of NK-cell therapies with existing treatments, such as chemotherapy or other immunomodulatory agents, to improve long-term efficacy. Preliminary preclinical studies indicate that administering NK cells alongside anti-GD2 antibodies significantly enhances survival rates in high-risk neuroblastoma cases, according to Rados.

Conclusion

The role of NK cells in tumor defense is highly complex, and their therapeutic application in solid tumors like neuroblastoma is still in its early stages. Nevertheless, ongoing research is paving the way to unlocking their full therapeutic potential and integrating them more effectively into clinical practice. “The coming years will be crucial in determining how NK-cell-based therapies evolve in clinical settings,” emphasizes Taschner-Mandl.

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How collaboration drives innovation… with Florian Grebien

Collaborations are essential in the world of science. In addition to the exchange of knowledge and technologies, they also offer valuable insights into different cultural and methodological approaches to research. This view is shared by Florian Grebien, Principal Investigator (PI) of the Biology of Pediatric Leukemia Oncoproteins research group at St. Anna CCRI.

In the world of biomedical research, collaboration between specialized research groups is becoming increasingly important. Although different research approaches and technologies can make collaboration challenging, Florian Grebien sees this as an opportunity to find innovative solutions. His team therefore works closely with several groups within the St. Anna Children’s Cancer Research Institute. Their aim is to conduct joint research to identify the molecular mechanisms of hematologic malignancies.

This collaboration between groups is an ideal way for young researchers to build up a network. Weekly research seminars and joint laboratory meetings provide an open atmosphere that encourages exchange and networking between colleagues. In general, Florian Grebien has clear advice for aspiring cancer researchers: “Don’t wait for your PI to introduce you to someone, but actively approach other scientists yourself. Every scientist loves to talk about their research – don’t be shy!”

To what extent do interdisciplinary collaboration and knowledge exchange play a role in your research?

Exchange of knowledge is an integral part of our research program. Ever since I started my independent career, I actively engaged in collaborations, and they have always been highly enriching. Collaborations are not only important to exchange reagents, technologies and/or knowledge, but they also provide access and insights into other cultures and strategies of performing research, which can be very interesting. Interdisciplinary collaborations are becoming increasingly important. While I find these types of collaborations particularly interesting, they are also challenging, as researchers from different fields often use very different approaches that are not always easy to integrate.

How has the importance of collaboration changed due to technological advances?

The increasing degree of specialization in biomedical research makes collaborations central and necessary for every original and successful research project. Without them, we would not be able to keep up with the pace at which critical technologies develop, and we need to keep embracing technological advance, as this is a key aspect of biomedical research.

What specific projects or research topics connect you and your research group with other groups within the St. Anna CCRI?

Within St. Anna CCRI, we cooperate very closely with the groups of Davide Seruggia, Kaan Boztug and Michael Dworzak, as we share a common interest in hematological malignancies and their molecular mechanisms. Beyond that, I enjoy discussions with Eleni Tomazou and Heinrich Kovar, as they work on related aspects in a different cancer context. It is interesting to see how researchers in different fields approach similar questions.

What do you value about working with the other groups?

I enjoy that within St. Anna CCRI, every PI shares the dedication and enthusiasm to contribute to a better understanding of pediatric cancer, as this will help to generate better therapies in the future. In addition, the translational/clinical background of some of the St. Anna CCRI groups is a source of inspiration for me to identify novel problems that are worth tackling.

What are your tips for young researchers who are just starting to build a network?

The most important advice I have for young researchers is to actively approach other scientists. Every researcher loves to talk about their work. Do not wait until your PI or somebody else establishes a connection – do it yourself! Do not be shy! At St. Anna CCRI, several opportunities exist to do that, such as the weekly research seminar on Wednesday, or joint lab meetings that are held by different groups. In addition, the building is small, which makes interactions easier.

How would you assess the importance of international collaborations for the success of your research group?

In retrospect, our engagement in international collaborations cannot be overestimated for the success of my research group. Several long-standing interactions, publications, grant applications and other joint activities started from a chat with a stranger during the coffee break at a conference. I would not have been able to achieve the same without these interactions.

Which other national or international research institutes do you work with as part of your research activities?

We entertain many collaborations with other academic institutions in Austria and beyond. In the Vienna area, our most important partners are the Medical University Vienna, the CeMM and the IMP.

Women in Science: Researchers Shaping the Future

Science thrives on curiosity, perseverance, and the passion to better understand the world. Yet, for many women, the path to a career in research has not always been straightforward. Stereotypes, structural barriers, and a lack of role models still discourage some girls from considering a future in science. However, women are essential in scientific fields—they shape research, drive innovation, and ensure that discoveries are approached from diverse perspectives.

At St. Anna Children’s Cancer Research Institute (St. Anna CCRI), female scientists work in various fields to improve the future for children with cancer. They study the genetic foundations of cancer, develop new therapeutic approaches, and investigate the mechanisms behind specific types of cancer. Their work requires precision, creativity, and perseverance—but the prospect of making real progress makes it all worthwhile.

Martha Zylka – A Passion for Molecular Biology

Her advice to young women in science:
“Do not compare yourself to others. Don’t let anyone intimidate you, follow your own path, be authentic, and always stay true to yourself and your values.”

Martha is a PhD student in the Kovar group researching lung metastases in pediatric patients. Her daily work is a combination of laboratory research, cell cultures, and data analysis. She finds the greatest joy when an experiment finally works after long optimization efforts, leading to new insights. For her, science is a continuous learning process—failures are part of the journey, but they also offer opportunities for growth.

Dr. Eleni Tomazou – Leading a Research Team

Her advice to young women in science:
“I would say to women in science to have confidence in themselves and if they need help and support, to go for it. Dream big and go for it!”

As a Principal Investigator, Eleni Tomazou leads a team of scientists investigating cancer mechanisms. She no longer conducts experiments herself but focuses on coordinating research efforts, writing grant applications, and ensuring that scientific findings are published. She describes science as demanding but incredibly exciting — the opportunity to gain new knowledge and perhaps even save lives is what drives her most.

Anna Hurt – The Importance of Laboratory Work

Her advice to young women in science:
“Science is not easy—it requires a lot of time and energy. But it is incredibly rewarding and a valuable experience that cannot be compared to any other profession.”

Anna Hurt works as a technical assistant in research. What matters most to her is that her work can have a direct impact on the lives of children. In the lab, she helps ensure that research findings can be translated into practice. From her own experience, she knows that people don’t always realize from the beginning whether science is the right path for them—it often becomes clear only when working hands-on in a research team.

Dr. Anna Hakobyan – The Fascination of Bioinformatics

Her advice to young women in science:
“If a young girl is even considering a career in science, then she should absolutely pursue it! That means she has already recognized how exciting it is to explore nature and better understand reality.”

Anna Hakobyan is a postdoctoral researcher specializing in computational analysis of biological data. Her work involves developing and testing new bioinformatics methods to decipher complex genetic information. Every day, she learns something new—one of the greatest joys of her profession. She especially appreciates collaborating with other researchers and working on something that extends far beyond her own desk.

Mirella Larch – Bridging Diagnostics and Research

Her advice to young women in science:
“Don’t lose faith in yourself! Talk to colleagues, seek feedback, and keep going. Don’t be discouraged—we need women in science, and you won’t regret it!”

Mirella Larch is a biomedical analyst. Her work combines laboratory diagnostics with research, always with the goal of achieving the best possible treatment outcomes for children with cancer. For her, the most rewarding moments are when a treatment is successful, when a child remains in remission for years—or, in the best case, is completely cured. 

Very Rare Subtype of Childhood Leukemia Characterized

A team at the St. Anna Children’s Cancer Research Institute (St. Anna CCRI) has headed an international collaborative study to characterize a very rare subtype of childhood B-cell acute lymphoblastic leukemia. The results, recently published in the journal Leukemia show that patients with this subtype need optimized therapy.

The treatment of B-cell acute lymphoblastic leukemia (B-ALL), the most common cancer in children and young adolescents, is a success story of modern medicine with cure rates approaching 90%. However, despite these achievements, irrespective of the treatment protocols used, 10-15% of patients still face relapse and subsequently a poorer prognosis, as only about 50% of all children with relapsed ALL can be cured. Therefore, to further improve outcome, it is essential to filter out subtypes of the disease with high relapse rates and to optimize front-line treatment.

In this international study 50 patients with a very rare genetic subtype harboring a PAX5::AUTS2 fusion gene who were treated with different therapy protocols were collected. Outcome analysis showed that the 5-year cumulative incidence of relapse for all patients was 48.0±7.8% and the event-free and overall survival rates 47.9±7.6% and 76.2±7.1%, respectively. The main risk factors were a younger age below 18 months and measurable residual disease after the first weeks of treatment.

International Collaboration is Key to Success

“Our study shows that patients with PAX5::AUTS2 B-ALL have a very high relapse rate and consequently a rather poor overall survival. Notably, especially infants and toddlers are affected by this disease subtype, with over 80% of patients under the age of three, and in many patients the disease spreads to the central nervous system,” explains Sabine Strehl, Principal Investigator at St. Anna CCRI, the disease characteristics. This subtype of B-ALL is so rare that it has so far not been described in detail, and it has taken a major international effort to collect sufficient cases for meaningful analysis.

World map highlighting austria in red and collaborating countries in yellow
The highlighted countries collaborated to collect enough cases for a meaningful analysis.

“Fifty cases may sound like a limited number, but for a rare childhood leukemia entity it is quite a lot, and every single case counted. Without the excellent collaboration between several European countries, especially with France, who contributed most patients, Italy, Poland, the Netherlands, Germany, the United Kingdom and the Czech Republic, as well as with Brazil, India, and Uruguay this study would not have been possible” adds Sabine Strehl.

The detailed analysis of the data showed that even in PAX5::AUTS2 leukemia patients enrolled in contemporary clinical trials, the relapse rate did not improve, indicating that these patients need special attention and that front-line treatment with the most advanced therapy options needs to be considered.

“This study will help to further improve the cure rates of childhood leukemia and ensure that every patient, no matter how rare their disease subtype, receives the most appropriate therapy,” concludes Sabine Strehl, who has long been interested in the prognostic relevance of rare genetic alterations in leukemia.

Publication:
Caye-Eude A, Fazio G, Pastorczak A, Boer JM, Steinemann D, Ganguli D, Sonneveld E, Haslinger S, D’Andrea L, Bradtke J, Lopes BA, Zaliova M, Escherich G, König M, Fortschegger K, Inthal A, Stasevich I, Emerenciano M, Trka J, Castillo L, Parihar M, Moorman AV, Bergmann AK, den Boer ML, Młynarski W, Cazzaniga G, Cavé H, Nebral K, Schinnerl D, Strehl S. PAX5::AUTS2 childhood B-ALL: a relapse-prone genetic subtype with frequent central nervous system involvement and a poor outcome. Leukemia. 2024 Dec 19. doi: 10.1038/s41375-024-02502-5.

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Epigenetics Brings Hope for New Therapies

Epigenetics is a key area of pediatric cancer research. Scientists are investigating molecular drivers of tumors, hoping to discover new therapies through these approaches. St. Anna Children’s Cancer Research Institute (St. Anna CCRI) has long focused on epigenetics and recently hosted a networking meeting on the topic.

Adult tumors often exhibit numerous DNA mutations that drive the hallmarks of cancer: uncontrolled growth, invasion of surrounding tissue, and evasion of the immune system. Pediatric cancers also display these characteristics but with far fewer DNA mutations. This is where epigenetics comes into play. Researchers study molecular “switches” that can turn genes on or off, influencing cancer development.

Findings like these are crucial in developing novel treatment strategies targeting such changes—potentially leading to gentler therapies for affected children. Epigenetic research is highly relevant, as many questions remain unanswered. To address this, St. Anna CCRI has established multiple research groups dedicated to the field. To foster international collaboration, the St. Anna CCRI Symposium Cancer Epigenetics was recently held at the Van Swieten Hall of the Medical University of Vienna. The meeting was organized by Davide Seruggia, Eleni Tomazou, Florian Grebien and Kaan Boztug, all Principal Investigators at St. Anna CCRI.

How Does Cancer Develop?

The work of Paola Scaffidi and her team at the Department of Experimental Oncology of the European Institute of Oncology (IEO) in Milan shows how epigenetic changes through the function of enhancers, genetic instability and interaction with the tumor environment influence cancer development. In her presentation, she emphasized that the combination of these is the disease driver. You could say that if a gene is the content of a letter, the enhancers are the address on the envelope. Which specific cells are the recipients of the message? And mutations in enhancers can have dramatic effects: A message is sent to the wrong tissue in the body, it is delayed or lost altogether. A kind of chain reaction is triggered during which cellular “brakes”, so-called tumor suppressor genes, are silenced. The cells lose the ability to repair themselves or die in a controlled manner – which contributes to tumor formation.

The scientist Paola Scaffidi stands behind a speakers desk presenting her research
Paola Scaffidi ©St.Anna CCRI

The scientist Judith Zaugg stands behind a speakers desk presenting her research
Judith Zaugg ©St.Anna CCRI
What Are Enhancers?

Judith Zaugg, Professor of Molecular Medicine at the University of Basel, leads a research group focused on enhancers. She investigates how errors in these enhancers—caused by genetic changes or external influences—can trigger diseases such as cancer or genetic disorders. Zaugg reported that her team employs computational methods to understand how DNA is regulated and how these processes influence disease development.

Which Gene Might Cause Medulloblastoma?

The research of Alexis Kentsis and his team at Memorial Sloan Kettering Cancer Center suggests that a gene called PGBD5 plays a key role in certain pediatric cancers, particularly medulloblastoma, a brain tumor occurring in the posterior region of the skull. PGBD5 can cause specific DNA breaks and rearrangements, leading to mutations in genes that control tumor growth.

The scientist Alex Kentsis stands behind a speakers desk presenting his research
Alex Kentsis ©St.Anna CCRI

The scientist Iannis Aifantis stands behind a speakers desk presenting his research
Iannis Aifantis ©St.Anna CCRI
How Can Cancer Cells Be Weakened?

Iannis Aifantis from the NYU School of Medicine studies how the genome is organized and the role of these structures in a particular type of blood cancer (acute T-cell leukemia, T-ALL). Aifantis and his team discovered that 3D chromatin hubs activate certain genes that promote cancer cell survival. But what exactly are 3D chromatin hubs? These are regions in the cell nucleus where multiple DNA segments cluster closely together, collectively regulating gene activation or suppression. Aifantis explained that a specific regulatory gene, MYB, plays a central role: blocking it can weaken cancer cells.

Young Cancer Researchers at St. Anna CCRI

Two young Principal Investigators at St. Anna CCRI also presented their work during the symposium. Polina Kameneva studies the origins of neuroblastoma, a cancer that arises in nerve tissue. 49 % of all neuroblastomas develop near the adrenal glands, but the reasons for this remain unknown. To uncover the mechanism, Kameneva’s team examined adrenal gland development. They found that a high number of sympathetic nerve cells are present during early developmental stages and investigated how these cells change over time. Her work is supported by a prestigious FWF START grant.

The scientist Polina Kameneva stands behind a speakers desk presenting her research
Polina Kameneva ©St.Anna CCRI

The scientist George Cresswell stands behind a speakers desk presenting his research
George Cresswell ©St.Anna CCRI

George Cresswell then discussed how chromosomal instability—errors occurring when cells distribute their chromosomes during division—affects cancer progression. He reported on a study (Nature Cancer) that he carried out during his time at the Institute of Cancer Research (Sottoriva lab, London). It shows that a large variety of chromosomal changes at diagnosis correlates with faster tumor recurrence in a clinical study of prostate cancer. Cresswell applied these insights to pediatric cancers, emphasizing that childhood cancers follow unique developmental patterns. His preliminary findings suggest that chromosomal instability could also play a crucial role in the progression of pediatric kidney cancer.

Ultimately, all of this important research may lead to clinical applications. However, many more scientific studies are needed—driven by curiosity and perseverance—to answer a lot of open questions.

Breakthrough in Langerhans Cell Histiocytosis Research: Stem Cell Model Paves the Way for New Therapies

(Vienna, 16 December 2024) Scientists at St. Anna Children’s Cancer Research Institute (St. Anna CCRI) have achieved a milestone in the study of the rare and complex disease Langerhans Cell Histiocytosis (LCH). Using an innovative model based on induced pluripotent stem cells (iPSCs), they were able to comprehensively study the mechanisms of the disease for the first time. The groundbreaking results, published in the journal Blood, offer hope for new treatment strategies for those affected.

Langerhans Cell Histiocytosis (LCH) is a rare and complex disorder of the hematopoietic system, characterized by a wide range of symptoms, from self-limiting lesions to tumor-like damage in multiple organs, systemic inflammation, and progressive neurodegeneration. Until now, the lack of suitable models has severely limited research into the disease’s mechanisms.

A pioneering new study, published in the journal Blood, provides critical insights into the mechanisms of LCH and potential treatment strategies. A team led by Caroline Hutter—Group Leader at St. Anna CCRI, Medical Director of St. Anna Children’s Hospital, and Professor of Pediatric Oncology at MedUni Vienna—has successfully developed an in vitro model of LCH. By leveraging an innovative laboratory-developed model based on iPSCs, the need for animal testing has been eliminated.

The authors Raphaela Schwentner, Giulio Abagnale, Caroline Hutter, Wouter van Midden, Sebastian Eder, Philipp Ben Soussia-Weiss ©St. Anna CCRI

Innovative Stem Cell Model: A Breakthrough in Research

To develop the model, the researchers introduced the BRAFV600E mutation into human stem cells in the laboratory. This mutation, which is the most common genetic alteration in LCH, triggers changes in cell development, causing the cells to behave similarly to those found in LCH-associated tissue damage.
“Our research highlights how the BRAFV600E mutation drives key characteristics of LCH, including inflammatory responses and neurodegenerative damage,” says Caroline Hutter. “The iPSC model fills a critical gap in LCH research, allowing us to analyze the molecular mechanisms of disease progression in different cell types.” Co-senior author Sebastian Eder, clinical scientist and pediatric oncologist at St. Anna Children’s Hospital, adds, “This model provides an invaluable tool for studying disease mechanisms and testing new treatments.”

From Precursor Cells to Pathological Tissue Damage

Using their model, the researchers demonstrated that the BRAFV600E mutation causes profound changes during hematopoiesis (blood formation). It alters the way certain genes are read and utilized—a process known as transcriptional regulation. These changes cause specific precursor cells in the blood to develop into cells resembling those found in the diseased tissues of LCH patients.

Reversing Molecular Damage

A particularly significant breakthrough was showing that these disease-related changes are reversible. Using specialized drugs called MAPK pathway inhibitors (MAPKi), the molecular disturbances in the cells were reversed. This finding suggests that these drugs could potentially benefit LCH patients.

Mutant Microglia Drive Neurodegeneration: New Insights into LCH Complications


The team also investigated the interplay between mutant microglia (a type of immune cell in the brain) and neurons, revealing how the BRAFV600E mutation drives neurodegeneration. They found that these mutant microglia cause significant damage to neurons and release substances that serve as markers for neurodegeneration. “Neurodegeneration is currently the most severe complication in the treatment of LCH,” explains Raphaela Schwentner, co-first author of the study. “With this system, we can study interactions between various cell types, such as neurons that are otherwise difficult to investigate, and hopefully develop new therapeutic approaches.”

This study represents a significant advance in understanding LCH and offers new hope for patients with severe and treatment-resistant forms of the disease. Through cutting-edge stem cell technology, the researchers have created a versatile tool for mechanistic studies and drug development. “Our model demonstrates the versatility of iPSCs in translational research,” says Giulio Abagnale, co-first author of the study. “We hope our work will improve the lives of LCH patients and their families.”

Neurons differentiated from iPS cells (in green) in co-culture with microglia cells (red)_© St. Anna CCRI

Publication

Abagnale G*, Schwentner R*, Ben Soussia-Weiss P, van Midden W, Sturtzel C, Pötschger U, Rados M, Taschner-Mandl S, Simonitsch-Klupp I, Hafemeister C, Halbritter F, Distel M, Eder SK#, Hutter C#. BRAFV600E induces key features of LCH in iPSCs with cell type-specific phenotypes and drug responses. Blood. 2024 Dec 4:blood.2024026066.
doi: 10.1182/blood.2024026066.

(*Co-Erstautoren, #Co-korrespondierende Autoren)

Press release_Breakthrough in Langerhans Cell Histiocytosis research_stem cell model paves the way for new therapies_StAnnaCCRIDOWNLOAD

‘Working together’ with Sabine Strehl

In today’s biomedical research, interdisciplinary collaboration is essential. While leukemia is the most common childhood cancer, certain subtypes are extremely rare necessitating international studies for comprehensive data collection to understand their pathogenesis and prognostic relevance. Sabine Strehl’s research focuses on unraveling the genetic mechanisms behind leukemia development, emphasizing the importance of robust research data and to collaborate with experts from different disciplines to achieve success.

Sabine Strehl has been at St. Anna Children’s Cancer Research Institute since its foundation and is the Principal Investigator of the Genetics of Leukemia Group. Together with her team, she aims to decipher the genetic mechanisms responsible for the development and progression of leukemia. To this end, her research group is deeply engaged in the molecular characterization of leukemia to gain a better understanding of the disease with the ultimate goal to develop new, targeted therapies. The exchange with other scientists is central to this effort: only through close collaboration with bioinformaticians, data scientists and oncologists can complex data sets be generated and analyzed, which is essential for addressing key questions of leukemia genetics.

Sabine Strehl advises young researchers to present their work at national and international conferences to get expert feedback. At St. Anna CCRI, networking opportunities abound through internal seminars, lectures by invited speakers, and social events, all of which lay the ground for scientific cooperation.

Science Communication Team: To what extent do interdisciplinary collaboration and sharing knowledge play a role in your research?

Sabine Strehl: “Walking in each other’s shoes” we, the experimental researchers, work side-by-side with bioinformaticians to better understand the pathogenesis and progression of leukemia. Bringing together our different backgrounds and expertise across disciplines opens up new perspectives to address challenging biomedical questions.

Science Communication Team: To what extent has the importance of collaboration changed due to/because of technological progress?

Sabine Strehl: The growing use of next-generation sequencing approaches to tackle unsolved biological questions along with the complexity of the resulting data demand strong teamwork with data scientists. From the earliest stages of project development, we work closely with bioinformaticians and computer scientists to formulate questions and plan the experimental designs. This mode of collaboration is key for generating meaningful functional genomics datasets and integrative data analysis.

Science Communication Team: Which specific projects or research topics connect you and your research group with other groups within St. Anna CCRI?

Sabine Strehl: We are currently modeling fusion protein-driven acute megakaryoblastic leukemia (AMKL) by combining CRISPR/Cas9 genome editing with in vitro differentiation of human induced pluripotent stem cells toward hematopoietic stem and progenitor cells. To understand the trajectories of leukemia development, we are applying functional genomics assays, including single-cell RNA-seq, ATAC-seq, ChIP-seq and the Developmental Cancer Genomics team of Florian Halbritter conducts the integrative bioinformatics analyses.

Together with the Immunological Diagnostics group of Michael N. Dworzak, by predicting cell surface antigen expression via whole transcriptome expression profiling, we aim to refine the correlation between underlying genetic alterations and the characteristic immunophenotypic features of the leukemic blast cells determined by flow cytometry. This endeavor not only aims to guide genetic analysis but also to improve disease classification and to identify markers for sensitive and robust leukemia detection to monitor measurable residual disease, a mainstay of risk stratification, as well as targets for immunotherapy.

Science Communication Team: What do you appreciate about working with the other groups?

Sabine Strehl: Joint brainstorming and bouncing ideas are both creative and fun. The beauty of working with other groups lies in interacting with people from diverse disciplinary backgrounds and to look at scientific questions from different angles, which broadens your horizon and increases the chances of success.

Science Communication Team: What advice do you have for young researchers who are just starting to build up a network? Are there opportunities to network at St. Anna CCRI?

Sabine Strehl: Participating in national and international meetings early in your career offers a valuable opportunity to present your work and receive feedback from experts in the field, and to network with peers in the scientific community. At St. Anna CCRI, attending internal seminars and lectures by invited speakers is key for learning about scientific questions and the approaches different research groups take to address them. While you don’t need to be best friends with everyone, knowing your colleagues personally facilitates communication, hence, attending social events and going out for dinner or a drink with colleagues once in a while will also foster scientific collaborations.

Science Communication Team: How would you rate the importance of international cooperation for the success of your research group?

Sabine Strehl: Although leukemia is the most common childhood malignancy, it is still a rare disease and international collaborative research projects often yield insights beyond what any single team could achieve alone, such as addressing the prognostic relevance of rare leukemia subtypes to refine risk stratification and optimize therapy. Cooperation and teamwork across organizational and cultural boundaries force you to look beyond your own nose and expand the potential for discovery and success.

Sabine Strehls research activities

Genetic Defect in Secondary Immune Organs Causes Life-Threatening Infections in Children

Bernhard Ransmayr and Kaan Boztug are first and last authors of the study.

(Vienna, November 22, 2024) An international team led by Kaan Boztug, MD has identified a new form of a rare disease that affects secondary lymphoid organs, shedding light on the significance of these structures for the human immune system. The discovered genetic defect leads to either the absence or significant dysfunction of these organs in several children. As a result, affected children suffer from recurring, life-threatening infections. The findings, published in Science Immunology, could significantly improve treatment options for patients with similar diseases.

Over the past years, the research group led by Univ.-Prof. Dr. Kaan Boztug has identified several rare genetic immune system disorders, characterizing the functions of key components of the immune system. Their work has also provided substantial new insights into the connection between immune deficiencies and the susceptibility to developing childhood tumors. Boztug, an expert in rare diseases, is the scientific director of the St. Anna Children’s Cancer Research Institute (CCRI), and conducts research at the Medical University of Vienna (MedUni Vienna) and CeMM, the Research Center for Molecular Medicine of the Austrian Academy of Sciences.

A New Type of Disease

The current study, conducted in collaboration with leading centers in Istanbul and Ankara, describes a novel rare disease that is remarkable in multiple ways. “In the DNA of the affected individuals, we identified mutations in the LTβR gene, which encodes the lymphotoxin-beta receptor (LTβR),” explains Dr. Bernhard Ransmayr, the study’s first author and a PhD student in Kaan Boztug’s laboratory. The patients lack all lymph nodes, including tonsils, and have a non-functional spleen. However, these secondary lymphoid organs are essential for activating the immune system and facilitating the differentiation, proliferation, and maturation of specialized immune cells. Consequently, these patients are unable to produce a sufficient quantity of protective antibodies.

Artificial Environment provides insights

Interestingly, the immune cells themselves are not directly affected by the genetic defect but are instead indirectly impaired due to the absence of the supportive environment provided by the secondary lymphoid organs. This was demonstrated by the team through laboratory experiments that mimicked the structure and function of lymph nodes. In this artificial environment, cells from the patients could develop normally into antibody-producing immune cells (B cells). This finding highlights the fundamental importance of interactions between surrounding cells (stromal cells) and immune cells for establishing an effective immune defense.

From Immune Genetics to Precision Medicine

Boztug emphasizes, “The discovery of the LTβR defect marks a significant advancement in our understanding of the architecture of immune organs and their role in human health. It illustrates how basic research can directly contribute to improving the lives of patients with rare diseases. Patients with LTβR mutations benefit from specialized care at immunodeficiency centers and corresponding medical support for their immune defense. A key insight from this research is that bone marrow transplantation—an established treatment for other immune deficiencies—would not succeed here, as the defect lies not within the immune cells themselves but in the structural components of lymphoid organs.” Future research aims to further decode the molecular mechanisms of LTβR within the human immune system and to develop potential therapeutic options.

Publication

 LTβR deficiency causes lymph node aplasia and impaired B-cell differentiation Bernhard Ransmayr M.D., Sevgi Köstel Bal, M.D., Ph.D., Marini Thian, Ph.D., Michael Svaton, M.D., Ph.D., Cheryl van de Wetering, Ph.D., Christoph Hafemeister, Ph.D., Anna Segarra-Roca, M.Sc., Jana Block, Ph.D., Alexandra Frohne, M.Sc., Ana Krolo, Ph.D., Melek Yorgun Altunbas, M.D., Sevgi Bilgic Eltan M.D., Ayca Kıykım, M.D., Omer Aydiner, M.D., Selin Kesim, M.D., Sabahat Inanir M.D., Elif Karakoc-Aydiner, M.D., Ahmet Ozen M.D., Ümran AbaM.Sc., Aylin Çomak M.D., Gökçen Dilşa Tuğcu, M.D., Robert Pazdzior, Ph.D., Bettina Huber, Ph.D., Matthias Farlik, Ph.D., Stefan Kubicek, Ph.D., Horst von BernuthM.D., Ph.D., Ingrid Simonitsch-Klupp., Marta Rizzi, M.D., Ph.D., Florian Halbritter, Ph.D., Alexei V. Tumanov, M.D., Ph.D., Michael J Kraakman Ph.D., Ayşe Metin, M.D., Ph.D., Irinka Castanon Ph.D., Baran Erman Ph.D., Safa Baris, M.D., Kaan Boztug.D.

Press release
Genetic Defect in Secondary Immune Organs Causes Life-Threatening Infections in Children _ StAnnaCCRI Press ReleaseHerunterladen

Collaboration with Davide Seruggia

In biomedicine, collaboration is more than a buzzword—it’s an essential component of advancing our understanding of complex diseases. As technology and scientific knowledge evolve, the scope of research has expanded to include numerous specialized fields, each bringing unique insights and tools. Consequently, biomedicine relies increasingly on interdisciplinary research groups, where scientists from diverse backgrounds pool their expertise. This cross-disciplinary approach allows researchers to tackle major challenges, such as cancer, with a level of precision and innovation that would be unachievable for individual scientists working in isolation.

“Scientific questions can be answered faster and more precisely if you rely on the expertise of collaborators”, Davide Seruggia emphasizes. Him and his team at St. Anna CCRI focus on pediatric leukemia. They study genetic and epigenetic factors—specific “switches” in DNA that drive cancer cell growth. Their goal is to uncover new, targeted treatments. For Seruggia, collaboration is essential to advancing the fight against childhood leukemia.

Interview

Science Communication Team: To what extent do interdisciplinary collaboration and sharing knowledge play a role in your research?

Davide Seruggia: Collaboration and knowledge exchange are fundamental to today’s science. It is unrealistic for one investigator to master all the disciplines that are necessary for a big discovery in science, including cell biology, genomics, statistics, mathematical modeling, polymer physics… But through collaboration, all these skills come together in one group of collaborative scientists.

Science Communication Team: To what extent has the importance of collaboration changed due to technological progress?

Davide Seruggia: I believe the complexity of both science and technology has been increasing constantly. Hence, collaboration was important in the past and will continue to be important in the future. Those are two parallel lines that should never cross. This way, research will always benefit and lean towards new, more complex, more accurate technology.

Science Communication Team: Which specific projects or research topics connect you and your research group with other groups within St. Anna CCRI?

Davide Seruggia: Together with the Halbritter group, we are combining hematopoietic stem cell differentiation with genomics and machine learning to learn better ways of obtaining mature cells in vitro. With the Boztug group, we are creating mouse models carrying the exact same mutations found in individuals with rare diseases. With the Grebien group we are focusing on a family of DNA-binding proteins and we are using sophisticated genome editing to study their role in AML. Our group is particularly interested in profiling the epigenome, and we often help other investigators at St. Anna CCRI that are interested in setting up assays for their experiments. As our group has access and expertise with mouse models, we collaborate with the Tomazou group in testing new models of Ewing Sarcoma in vivo.  

Science Communication Team: What do you appreciate about working with the other groups?

Davide Seruggia: Collaboration multiplies research output. Scientific questions can be answered faster and in a more precise way, if you count on your expertise and on that of collaborators in the building. In addition, collaboration forces us to be more rigorous with our science.

Science Communication Team: What advice do you have for young researchers who are just starting to build up a network?

Davide Seruggia: What triggers collaboration is curiosity, generosity and communication. To start the engine of collaborative work, one must first offer help to a colleague that might benefit from an idea or a technology you master. The next time, maybe help will come spontaneously to your door.

Science Communication Team: How would you rate the importance of international cooperation for the success of your research group?

Davide Seruggia: International collaborations are highly important. My group is involved in a large consortium focused on gene regulation, the NIH IGVF. Through that, we are exposed to state-of-the-art science and technology of the field, world-wide. Sometimes we have to adjust our schedule and align with the time differences, but it is absolutely worth the effort. In the context of pediatric leukemia and particular subtypes we are interested, international collaboration is key in order to access to information, and widen our cohorts and sample size.

Research activities of the Seruggia group 2024

How to Combat Fungal Infections in Immunocompromised Patients?

(Vienna, 17. 10. 2024) A new study from the St. Anna Children’s Cancer Research Institute (St. Anna CCRI) warns of the hidden dangers of invasive fungal infections in immunocompromised patients. The international research team, led by scientists Chantal Lucini, Klára Obrová, and Thomas Lion, has found that while prophylactic treatments with antifungal drugs can significantly reduce the risk of fungal infections in patients undergoing intensive chemotherapy or stem cell transplantation, they also introduce new challenges. The study was recently published in the prestigious Journal of Hematology & Oncology and has garnered significant attention in the medical community.

Invasive fungal infections pose a substantial threat to individuals with weakened immune systems, as their bodies are often unable to combat these dangerous pathogens. Clinical practice relies on prophylactic antifungals, administered to prevent the onset of infections. However, the current study reveals that this approach is not without risks: on one hand, the drugs used are often toxic and expensive, and on the other hand, prophylactic treatment is increasingly leading to so-called breakthrough infections. These are caused by previously rare fungal species that are resistant to the antifungals in use, making these infections particularly difficult to diagnose and treat.

To address this challenge, the research team developed new molecular detection methods based on the “panfungal” PCR technology. This patented method allows for the quick and sensitive detection of over 100 different fungal species, including those that cannot be identified using traditional diagnostic procedures. These advanced tests are particularly valuable as they enable not only the rapid identification of pathogens but also the detection of rare fungi that can cause life-threatening infections in immunocompromised patients. Early treatment of invasive infections caused by clinically relevant fungi is crucial for successful outcomes.

Not Every Infection Requires Treatment

The study included a multicenter investigation of 195 pediatric and adult high-risk patients, many of whom were cancer patients undergoing intensive chemotherapy or allogeneic stem cell transplantation. A total of 935 blood samples were analyzed, revealing that in many cases, DNA from plant-associated fungi, which are usually considered harmless, was detected. This highlights a key finding of the study: not every detected fungal infection automatically requires treatment. It is essential to accurately determine which fungi are actually dangerous, to enable rapid treatment where necessary while avoiding unnecessary and burdensome therapies.

Detection is not enough

The research team emphasizes that while molecular screening methods are a powerful tool, they must be used with caution. Accurate identification of fungal species is crucial to ensure that only potentially dangerous infections are treated, thus avoiding unnecessary medical interventions. This balance is critical to optimize the treatment of high-risk patients, such as children undergoing cancer therapy.
Thomas Lion, group leader at the St. Anna CCRI and medical director of the affiliated Labdia Labordiagnostik GmbH, summarized the significance of the findings: “Our research shows that the use of broad screening methods carries a great responsibility. It is not enough to simply detect the presence of fungal DNA; identifying the specific fungal species is crucial to choosing the right treatment and reducing the risk of unnecessary therapies.”

This study represents a significant advance in understanding and managing invasive fungal infections in immunocompromised patients. It highlights the need to critically assess molecular diagnostic methods to distinguish between harmless and dangerous fungi. In the long term, this could improve clinical care for cancer patients by enabling more targeted, life-saving treatments while reducing side effects and unnecessary therapies.

The study was conducted as part of the EU-funded FUNGITECT project, underscoring the importance of European collaboration in medical research. The findings offer valuable new insights for clinics and medical professionals who face the daily challenge of protecting their immunocompromised patients from life-threatening infections while minimizing unnecessary risks.

Paper:
Lucini C, Obrová K, Krickl I, Nogueira F, Kocmanová I, Herndlhofer S, Gleixner KV, Sperr WR, Frank T, Andrade N, Peters C, Engstler G, Dworzak M, Attarbaschi A, van Grotel M, van den Heuvel-Eibrink MM, Moiseev IS, Rogacheva Y, Zubarovskaya L, Zubarovskaya N, Pichler H, Lawitschka A, Koller E, Keil F, Mayer J, Weinbergerová B, Valent P, and Lion T. Prevalence of fungal DNAemia mediated by putatively non-pathogenic fungi in immunocompromised patients with febrile neutropenia: a prospective cohort study. J Hem Oncol 2024, 17: 63-8.

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ESCCA Conference 2024: Advancements in Clinical Cell Analysis

Margarita Maurer-Granofszky, researcher of the Dworzak group, was invited to present her research at the ESCCA Conference 2024. In her presentations, she highlighted the importance of detecting minimal/measurable residual disease (MRD) in children with acute myeloid leukemia (AML) and how new technologies like artificial intelligence (AI) can improve diagnostic accuracy.

The European Society for Clinical Cell Analysis (ESCCA) is one of the world’s leading organizations dedicated to the research and application of cell analysis. Every year, experts from around the globe gather at the ESCCA conference to present and discuss the latest scientific developments. The 2024 conference, held from September 25-28 in Palma de Mallorca, once again provided a platform for innovative technologies that play a critical role in diagnosing and treating serious diseases like cancer.

This year, Margarita Maurer-Granofszky, a researcher in the Dworzak Group, was invited to deliver two talks at the ESCCA conference. Her presentations focused on the detection of minimal/measurable residual disease (MRD) in children with acute myeloid leukemia (AML) and the global standardization of these crucial measurements. She specifically explored the use of flow cytometry and emerging approaches like AI to enhance the accuracy and reliability of results.

Margarita presenting her work at the ESCCA conference 2024.

What is flow cytometry and how does it work?

Flow cytometry is an advanced technique used to analyze individual cells in liquid samples. In this process, a sample is passed through a specialized device called a flow cytometer. As the cells pass one by one through a laser beam, the device measures properties such as size, shape, structure, and surface molecules. This detailed information allows for the identification of even rare cell types, such as cancer cells, within a sample.

One key advantage of flow cytometry is its ability to examine large numbers of cells in a short time, providing precise data. In cancer research, it is often used to monitor therapies and detect whether any cancer cells remain in a patient’s body. This technique offers valuable insights into disease progression and helps doctors tailor treatments to individual patients.

Minimal Residual Disease (MRD) and Its Prognostic Importance

A central focus of Margarita’s research is the detection of minimal residual disease (MRD) via flow cytometry. MRD refers to the residual amounts of cancer cells that remain in the body after therapy, which are often undetectable by conventional diagnostic methods. Despite an apparently successful treatment, these remaining cancer cells can eventually lead to a relapse of the disease. Accurate MRD detection is therefore critical for improving long-term outcomes.

In pediatric AML, flow cytometry plays a key role in identifying these extremely small numbers of cancer cells. Early detection of MRD allows doctors to better predict the disease’s course and make potential adjustments to treatment, making MRD detection a vital prognostic factor that indicates how likely the leukemia is to return.

Standardization and New Technologies in MRD Research
Margaritha with her work about standardization.

In her talks, Margarita Maurer-Granofszky emphasized the need to standardize flow cytometric MRD measurements globally. Currently, differences exist in how these measurements are performed and interpreted across clinics and research institutions. A unified approach would ensure that results are comparable and reliable everywhere.

Another focus of Margarita’s research is the introduction of new technologies, such as the use of AI to analyze the vast amounts of data generated by flow cytometry. AI can help recognize patterns in the data and refine diagnoses. Along with stringent quality controls, this can further improve the reliability of MRD detection.

Margarita’s work at the ESCCA conference demonstrates how modern technologies and global collaboration in cell analysis are revolutionizing leukemia treatment and ultimately helping to improve the survival chances of affected children.

Student Applies AI in Cancer Detection and supports St. Anna CCRI

(Vienna, 21.08.2024) Alessandro Rodias, a student from the Sir Karl Popper School in Vienna has explored the potential of radiomics in cancer detection. Through his innovative project, he has demonstrated how artificial intelligence (AI) can be applied to analyze radiological images for improved cancer diagnosis.

Radiomics, an emerging field focused on the extraction and analysis of data from radiological images, offers enormous potential for medicine. Alessandro Rodias leveraged this technology to develop a method that allows essential prognoses, such as survival chances and metastasis risk, to be derived from a simple CT scan. By applying AI, he was able to conduct precise analyses that provide valuable information for medical diagnosis and treatment.

“You can, for example, run a simple CT scan through an AI and ideally predict survival chances, metastasis risk, etc., just from one image,” the student explains. His work has the potential to increase diagnostic accuracy and improve personalized treatment strategies.

With this outstanding work, he won 1,000 euros from the „JugendInnovativ Competition“ which he donated to St. Anna CCRI.

New Horizons: Internship in Boztug Group

But Alessandro’s commitment doesn’t stop there. He is now starting an internship in the research group of Scientific Director, Kaan Boztug. Here, he will have the opportunity to deepen his knowledge and actively participate in research projects. “In any internship, regardless of the institute, I find learning and understanding the background the most exciting,” says the student. “Working in pediatric cancer research and particularly in the Boztug lab is a fantastic opportunity for me. All aspects of lab work are extremely exciting for me right now.”

Creativity meets community spirit

This story impressively shows how young people can make a difference through dedication and creativity. The student from Sir Karl Popper School is a shining example of the importance of community involvement and innovative ideas to improve the world.

St. Anna CCRI is proud to support such inspiring young talents and benefit from their commitment. The student’s generous donation will help drive research forward and improve the chances of recovery for children with cancer. His contribution to science and his commitment to the community send a powerful message about the importance of supporting young researchers and continuously fostering innovations in medical research.

New Insights into Risk Factors for a Subtype of Acute Lymphoblastic Leukemia

A team around Sabine Strehl and Dagmar Schinnerl has made significant progress in studying a subtype of B-cell acute lymphoblastic leukemia. The research findings, recently published in the Blood Cancer Journal, shed new light on the specific characteristics and risk factors of this form of leukemia.

B-cell acute lymphoblastic leukemia (B-ALL) is the most common cancer in children and adolescents. While it is highly treatable today, further improvement in cure rates requires a deeper understanding of the risk factors for the various subtypes of B-ALL. In a large-scale study, samples collected over more than 20 years from 1,237 patients treated in Austria according to international therapy protocols were analyzed. Seventy cases of the so-called DUX4 subtype of B-ALL were identified. This subtype is one of more than 20 subtypes of this leukemia, characterized by specific genetic and immunological features. The DUX4 subtype is marked by gene fusions leading to the overproduction of abnormal forms of the DUX4 protein, which is inactive in normal blood cells, and a typical gene expression profile. Additionally, the leukemic cells carry the surface molecule CD371.

Sabine Strehl (last author) and Dagmar Schinnerl (first Author)

The study results show that patients with this form of B-ALL generally have a good prognosis. The 5-year survival rate is 95.1%, and the 10-year survival rate is 88.1%. However, risk factors have been identified that may worsen the prognosis, particularly the loss of certain DNA segments (IKZF1plus deletion profile) and mutations in the tumor suppressor TP53.

Collaboration of Research, Diagnostics and Clinic

“Our research shows that the risk factors for DUX4-positive B-ALL need to be better understood to optimize therapy,” says Sabine Strehl. The comprehensive analysis of the large number of patients was conducted in collaboration with Labdia Laboratory Diagnostics GmbH, a subsidiary of St. Anna CCRI, and the St. Anna Children’s Hospital. First author Dagmar Schinnerl emphasizes, “Without the collaboration of research, diagnostics, and clinic, this work would not have been possible. We are pulling together in the same direction to further optimize the treatment of acute lymphoblastic leukemia in children and adolescents.”

In addition to the IKZF1plus deletion profile and TP53 mutations, other important results of the study relate to the so-called swALL phenotype, in which leukemia cells transform into another type of blood cell resembling monocytes during the early phase of therapy. These patients also have a poorer prognosis, requiring an adjustment in the monitoring of minimal residual disease. On the other hand, an early poor response to therapy, usually indicative of a high risk, appears to be less relevant for patients with DUX4 B-ALL.”Our findings highlight the need to revise the current prognostic factors and risk stratification parameters for DUX4 patients,” say Strehl and Schinnerl. “It is too early to make a therapy recommendation. Our data still need to be confirmed in independent studies,” the authors acknowledge, “but we provide a roadmap of what factors need to be examined in detail.”

Publication
Schinnerl D, Riebler M, Schumich A, Haslinger S, Bramböck A, Inthal A, Nykiel M, Maurer-Granofszky M, Haas OA, Pötschger U, Köhrer S, Nebral K, Dworzak MN, Attarbaschi A, Strehl S. Risk factors in DUX4-positive childhood and adolescent B-cell acute lymphoblastic leukemia. Blood Cancer J. 2024 Jul 22;14(1):119. doi: 10.1038/s41408-024-01099-3.

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