Research

AML represents 20% of pediatric leukemia, but accounts for most of disease-related mortality in children, due to chemo-resistance or relapse. Despite advances in risk stratification and hematopoietic stem/progenitor cell (HSPC) transplantation, overall survival rates in pediatric AML average 60-70%, and can be as low as 20% for the high fatality genotypes, reflecting a limited appreciation of the heterogeneity of the disease.

The Cellot lab has prioritized acute megakaryocytic leukemia (AMKL), a poor prognostic subgroup of infant AML associated with recurrent and mutually exclusive chimeric fusion oncogenes. Pediatric patient samples are rare, limiting our understanding of the disease, development of diagnostic biomarkers, and drug discovery.

We establish human models of high fatality pediatric AML using genetically engineered cord blood HSPCs (synthetic leukemias) to uncover genotype-specific molecular pathways, biomarkers and therapeutic vulnerabilities. In addition, we are studying the functional heterogeneity of normal HSPCs, synthetic leukemias, and primary specimens, to identify the cell of origin of high fatality pediatric leukemia. Finally, Dr Cellot and colleagues are participating to national initiatives for biobanking and genomic characterization of childhood cancers.

Current projects