Clonal evolution and biology of co-operative oncogenic events in acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) develops by a stepwise acquisition of mutations in immature lymphoid cells during which several leukemia clones appear and evolve. Using single-cell sequencing, we aim to obtain more detailed knowledge on the presence of the different leukemia clones at diagnosis and on their evolution during drug treatment. Accumulation of mutations in ALL also does not occur randomly, and particular lesions show significant co-occurrence or mutually exclusivity in the leukemia cells. In a second aim, we will study the molecular biological mechanisms by which co-occurring oncogenic events in T-cell ALL can potentially cooperate with each other to drive leukemia development, and how this can result in new vulnerabilities of the leukemia cells to drug treatment.Finally, a series of ALL cell and mouse models will be developed in this projects (xenografts and transgenic models), in which candidate drugs will be preclinically tested.

Keywords:acute lymphoblastic leukemia, single cell sequencing, clonal evolution, cooperation of mutations, targeted therapy

Disciplines:Morphological sciences, Oncology