Bone marrow sites differently imprint dormancy and chemoresistance to T-cell acute lymphoblastic leukemia
"In this project, we studied the development of human cells of acute T lymphoblastic leukemia (LAL-T) within a medullary microenvironment rich in adipocytes thanks to the use of immunodeficient mice. We have shown that the blasts of ALL -T nestled in this medullary environment (rich in adipocytes), become dormant and intrinsically resistant to drugs used in chemotherapy targeting the cell cycle. "(Cahu & Calvo et al., Blood Advances, 2017)
Increased vascular permeability in the bone marrow microenvironment contributes to disease progression and drug response in acute myeloid leukemia
"We are studying the microenvironment in bone marrow of mice transplanted with acute myeloid leukemia from patients with intravital multiphoton imaging coupled with transcriptomic analysis. We have observed increased vascular permeability, resistant to chemotherapy, associated with an increase in the endothelial compartment of nitric oxide and promoting leukemic progression to the detriment of hematopoietic stem cells "
THREE ORAL COMMUNICATION AWARDS
Alteration of VDR and BMP pathway in normal hematopoiesis and AML immature cells
"The prevention of relapses linked to the persistence of leukemic stem cells is a major issue in acute myeloid leukemia. My thesis project studies the involvement of the vitamin D receptor (VDR) in the control of normal and leukemic hematopoietic stem cells as well as the associated molecular pathways, including the Bone Morphogenetic Protein (BMP) pathway. "
T cell help mediated by IL2 orchestrates BACH2 downregulation that allows plasma cell differentiation
"The terminal differentiation of B lymphocytes requires the help of T lymphocytes. We have demonstrated that interleukin-2 secreted by T lymphocytes activates ERK / ELK1 and represses the expression of BACH2 by modulating the activity of its super enhancer, allowing the derepression of the transcriptional program at the origin of plasmocyte differentiation. "
Role of REL in drug resistance in chronic lymphocytic leukemia
"Gain in short arm of chromosome 2 (2p +) is a recurring anomaly in chronic lymphocytic leukemia (CLL). We have shown that gain in 2p was associated with poor prognostic factors (del11q, IGHV not mutated) and resistance to treatments. Our project consists in characterizing the genetic bases of this resistance by studying the role of oncogenes contained in the 2p region. "