Coordonnées
Centre de recherche, Hôpital Maisonneuve-Rosemont
5415, boulevard de l’assomption
Montréal (Québec) H1T 2M4
T 514-252-3400 #4674
Axes de recherche
- Immunologie et hématopoïèse
- Cancérologie
Description de la recherche
L’hématopoïèse clonale (HC) survient chez une proportion significative de la population vieillissante et est associée à un risque accru de cancers hématologiques et de maladie cardiaques. Nous avons décrit ce phénomène en 1996 (Blood) par des techniques basées sur l’inactivation du chromosome X. Nous avons déterminé que l’HC était en partie causée par l’acquisition de mutation somatique dans le gène TET2 (Nature Genet, 2012) et caractérisé sa prévalence et son impact sur la production sanguine en 2017 (Blood). Présentement nous étudions le rôle de l’inflammation (Nature 2018, Blood Advances, 2020) sur l’initiation de l’HC et la progression clonale. Nous sommes à déterminer s’il y a des prédispositions génétiques à l’HC par une approche de linkage génétique dans une cohorte de 230 familles.
Research axis
- Immunology and hematopoiesis
- Cancer
Research description
Clonal hematopoiesis (CH), which occurs in a large segment of the aging population has been clearly associated with predisposition to hematological cancer and cardiovascular disease. We first described CH 22 years ago, studying normal aging females using X-chromosome inactivation (XCI) skewing as a surrogate for clonality assessment (Blood 1996). We subsequently demonstrated that CH is partly caused by acquired somatic mutations in the TET2 gene (Nature Genet 2012). We further characterized CH using a gene-targeted approach in a large cohort of 2530 normal individuals. (Blood 2017). We are currently investigating the causal factors of CH by looking at inflammation biomarkers in large cohort (Nature 2018, Blood Advances 2020) and at its genetic predisposition by genetic linkage approaches.
Publications
- Busque L, Patel JP, Figueroa M, Vasanthakumar A, Provost S, Hamilou Z, Mollica L, Li J, Viale A, Heguy A, Hassim M9, Socci N, Gonen M, Mason CE, Melnick A, Godley LA, Brennan C, Abdel-Wahab O, Levine RL. Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis. Nat Genet. 2012 Nov 1;44(11):1179-81. doi: 10.1038/ng.2413. Epub 2012 Sep 23. PMID : 23001125.
- Buscarlet M, Provost S, Feroz Zada Y, Barhdadi A, Bourgoin V, Mollica L, Szuber N, Dubé MP, Busque L. DNMT3A and TET2 dominate age-associated clonal hematopoiesis, have benign hematological phenotypes but different genetic predisposition. Blood (2017) 130 (6), 753-762.
- Buscarlet M, Provost S, Feroz Zada Y, Vincent Bourgoin, Mollica L, Dubé MP, and Busque L. Lineage restriction analyses in subjects with CHIP indicates a strong myeloid proliferation bias for TET2 and a multipotent stem cell origin for DNMT3A. 2018 Jul 19;132(3):277-280 doi: 10.1182/blood-2018-01-829937. Epub 2018 May 15. PMID:29764839
- Meisel M, Hinterleitner R, Pacis A, Chen L, Earley ZM, Mayassi T, Pierre JF, Ernest JD, Galipeau HJ, Thuille N, Bouziat R, Buscarlet M, Ringus DL, Wang Y, Li Y, Dinh V, Kim SM, McDonald BD, Zurenski MA, Musch MW, Furtado GC, Lira SA, Baier G, Chang EB, Eren AM, Weber CR, Busque L, Godley LA, Verdú EF, Barreiro LB, Jabri B. Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host. Nature. 2018 May;557(7706):580-584. doi: 10.1038/s41586-018-0125-z. Epub 2018 May 16. PMID:29769727
- Ayachi S, Buscarlet M, Busque L. 60 Years of clonal hematopoiesis research: From X-chromosome inactivation studies to the identification of driver mutations. Exp Hematol. 2020 Jan 28. pii: S0301-472X(20)30029-1. doi: 10.1016/ j.exphem. 2020.01.008. [Epub ahead of print] Review. PMID: 32001340
- Lambert Busque, Maxine Sun, Manuel Buscarlet, Sami Ayachi,Yassamin Feroz Zada, Sylvie Provost,Vincent Bourgoin, Luigina Mollica, Marlies Meisel, Reinhard Hinterleitner, Bana Jabri, Marie-Pierre Dubé and Jean-Claude Tardif. High-sensitivity C-Reactive Protein is associated with Clonal Hematopoiesis of Indeterminate Potential. Blood Advances (2020), in press.