PIF2025 - Paving the Way to Prevention: Intercepting Childhood B Cell Leukemia Course - (PID2024-155590OB-I00)

Leukemia accounts for one third of all childhood cancers with B-cell acute lymphoblastic leukemia (B-ALL) representing the most frequent form of the disease. As cancer treatment has become more effective, a larger proportion of children with B-ALL survive; however, many suffer from treatment-associated late effects. Further, for those children whose B-ALL relapses, chances for survival are greatly diminished. Together, these facts render B-ALL a major public health concern and highlight the importance of preventive strategies. Recent studies have demonstrated that more than 5% of healthy children are genetically-predisposed to develop B-ALL and carry pre-leukemic cells in their body at birth. Nevertheless, these cells may persist for years, without developing into B-ALL. We and others have shown that exposure to specific environmental triggers promotes a ‘tipping point’ during which pre-malignant B-cells acquire critical secondary genetic lesions, thereby progressing to B-ALL (Cancer Discovery-2015; Nature-2017; Cancer Research-2017; Cancer Research-2018; EMBOJ-2018, Leukemia-2018; Trends in Cancer-2018; Nature Communications-2019; Blood-2020; Nature Communications-2023). Thus, at the heart of this research project lies our vision of applying highly conceptually and technically innovative approaches to tackle a fundamental clinical challenge: identifying and targeting these aberrant B cell clones before they undergo malignant transformation (Nature Reviews Immunol