Biology of Malignant Blood Disorders in Children

Objectives and Challenges

Malignant hematologic diseases account for nearly 45% of pediatric cancers. Among these, acute myeloid leukemias (AML) are associated with a poor prognosis, characterized by treatment resistance and frequent relapses. Our objective is to understand the fundamental mechanisms underlying these leukemias by identifying molecular alterations specific to pediatric cancers in order to characterize their functional consequences. The challenge is to identify specific vulnerabilities in leukemic cells to improve patient care.

Research Areas / Major Projects

We employ integrated approaches combining analyses of patient samples, cellular and pathophysiological modeling, and high-resolution molecular analyses. Patient-derived xenograft (PDX) models that accurately replicate the human disease and allow for the evaluation of preclinical approaches that closely mimic the clinical setting. In addition, transgenic models and human induced pluripotent stem cells (iPSCs) are used to reproduce early stages of development and to precisely introduce, via genome editing, the mutations observed in patients.

Our work relies on advanced cytometry, transcriptomics, epigenomics, and metabolomics—including at the single-cell level—to characterize the heterogeneity of leukemic cells and the molecular basis of tumor transformation. We actively collaborate with a national and international network of clinicians, biologists, and bioinformaticians (e.g., the PEDIAC, CONECT-AML, ALARM3, and Paris Kids Cancer programs).

Major Findings and Scientific, Clinical, and Societal Impacts

The team has identified several fusion oncogenes in pediatric AML, demonstrated the role of the stage of fetal development in leukemogenesis, and recently developed an iPSC-based model that replicates human leukemias and highlights the existence of mechanisms common to various pediatric cancers. Our research contributes to a better understanding of the developmental origins of childhood cancers and to the identification of new therapeutic targets, with the ultimate goal of improving patient survival and quality of life.