La génomique fonctionnelle de la leucémie myéloïde aiguë in vivo

 

François Mercier

CIUSSS du Centre-Ouest-de-l'Île-de-Montréal

 

Domaine : cancer

Programme Chercheurs-boursiers cliniciens - Junior 1

Concours 2019-2020

Acute myeloid leukemia (AML) is a very aggressive type of blood cancer. AML cases remain difficult to treat, with a survival rate of about 30%. AML treatments are highly toxic and often result in long-term side effects, including secondary cancers. In order to improve the treatment of AML, the goal of my research is to better understand its development and the main modifications that promote the growth of leukemic cells within their native environment, the bone marrow. Genetic changes seen in human AML can recreate the disease when they are introduced into mouse cells. These mouse models of AML recapitulate many features of human disease while being reproducible for research purposes. During my postdoctoral training, I developed approaches that measured leukemic growth in mice, and analyzed changes in gene expression or susceptibility to genetic manipulation using a new technique called CRISPR.

This allowed me to evaluate which genes are activated and essential in leukemic cells. Based on this approach, I now plan to leverage my dual research and clinical training to validate some of these new vulnerabilities and test their therapeutic potential. I will use a combination of experimental models and samples isolated from patients. In particular, we will focus on a set of adaptations in leukemic cell metabolism that we have identified as important for leukemic growth. In addition, we are using a new technology called single-cell RNA sequencing to analyze patient samples. Our goal is to identify adaptations of AML cells that become resistant to treatment and to find better ways to prevent the development of resistance.