Matthieu Duchmann’s team – Leukemia evolution and plasticity [LEAP]

Leukemic cells can adapt to therapy, promoting the persistence of rare residual cells that drive relapse. This research axis investigates these adaptive mechanisms by analyzing sequential patient samples collected before and during treatment using single-cell genomics technologies, to capture the stepwise dynamic stages of leukemic plasticity. These studies are conducted in prospective clinical trials involving patients treated with intensive chemotherapy (DYNHAEMICS study, NCT05304156), less intensive AZA/VEN therapy (DREAM study, NCT06225128), or ivosidenib (biological study within the IDIOME cohort, NCT06225128).

Even in remission, very rare tumor cells may persist and lead to relapse. We are developing single-cell multi-omics approaches to better characterize these rare residual leukemic cells. The goal is to identify therapeutic targets specific to these cells and to propose preemptive treatments, before cytological relapse. A clinical trial project aims to demonstrate the feasibility of this strategy and its potential to guide personalized treatments in the setting of measurable residual disease.