Team 16: (E. Delabesse): to understand how altered transcription factors drive leukemogenesis
The hematopoietic stem cell differentiation allow the production of blood cells. This process is finely regulated by extrinsic factors (adhesion molecules, cytokines) and intrinsic factors (transcription factors (TF)).
Deregulation of this process in the early stages of the differentiation can lead to the transformation of progenitor cells, leading to acute leukemia characterized by an early block of hematopoietic cell maturation (blasts) and an uncontrolled proliferation. We aim to:
- identify new TF alterations,
- study their influence on the normal differentiation and
- assess their role in the leukemic process.
Currently, major targeted therapies are targeting cytoplasmic pathways. In order to find new therapeutic targets, we aim to decipher the pathways relaying the PAX5 and GATA2 mutant oncogenic effects. To this purpose, we have in the past five years identified recurrent mutations of TF in patients with acute leukemia and, due to the high degree of conservation of TF between man and mouse, we are modeling these alterations at the cellular and animal levels.