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KFO 5010:  CATCH ALL Towards a Cure for Adults and Children with Acute Lymphoblastic Leukemia (ALL)

Subject Area Medicine
Term since 2022
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 444949889
 
Acute lymphoblastic leukemia (ALL) is the most common cancer in children and occurs also in adults. Current age-stratified therapy results in a long-term survival of up to 90% of children, which decreases to less than 50 % in older adults. It is largely unclear which factors define an almost linear relationship between increasing age and poorer outcomes emphasizing the clinical need for better therapies. Identifying mechanisms of disease persistence across age groups to guide age-overriding molecular-driven therapies is the unique contribution of the CATCH ALL clinical research unit. Irrespective of age, measurable residual disease (MRD) is the most important adverse prognostic factor in ALL and it is believed that the patient´s immune system plays a key role in keeping MRD in check. However, only few systematic studies have investigated the contribution of the immune system to controlling residual leukemia in ALL. We suspect that age differences in the immune control largely contribute to the distinct outcomes. CATCH ALL investigates age-specific immune-leukemia interactions in addition to the molecular dissection of the leukemic cells. During the first funding period, we established joint workflows enabling in-depth analyses with cross-functional, interdisciplinary teams as a clear advantage and a hallmark of CATCH ALL. In the second funding phase we will further consolidate and enhance our efforts towards novel molecular-driven and age-adapted therapeutic approaches, and to translate these into clinical care. Achieving this overarching goal requires a thorough understanding of ALL biology within the context of the immune microenvironment and the clinical presentation of the disease. To unravel the complex mechanisms driving disease persistence and immune control across age groups, a concerted effort is essential. The objectives of the second funding period of CATCH ALL will be addressed by eight closely interacting projects in conjunction with two central platform projects to coordinate comprehensive bioinformatics analyses and facilitate clinical application within the established nationwide CATCH ALL board. Using novel technologies we will gain insights into the spatial resolution and interplay between malignant cells and the adjacent microenvironment. This will provide us with an even more comprehensive understanding of disease biology and drug resistance, potentially allowing the identification of novel targets for (immuno)therapeutic intervention. Our established CATCH ALL infrastructure is based on the reference laboratories for the AIEOP-BFM and GMALL study groups, the national reference pathology center for pediatric lymphomas, and the IKMB with its DFG sequencing center (CCGA) and thus forms the strong translational research network for ALL. In the long term, CATCH ALL will make transformative contributions to fundamental mechanisms and novel treatment interventions of ALL, ultimately improving outcomes across all age group.
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