Drug resistance in hematological malignancies (DRIHM)

Director : 

Santos A. Susin

Deputy Director : 

Florence Nguyen-Khac

Through classical and high-throughput approaches, our research focuses on the analysis of the cellular and molecular mechanisms associated to drug resistance in different hematological malignancies. Our final goal is to propose original approaches to overcome the therapeutic blockade. The team leverages the patients with hematological disorders from the Pitié-Salpêtrière Hospital and has access to large cohorts through its involvement in various national and international clinical trials

 

Key Words: .Chronic Lymphocytic Leukemia; Metabolism; B-cell receptor; Drug resistance; genomic abnormalities; Intraocular and cerebral lymphomas; Systemic mastocytosis; Waldenström’s macroglobulinemia

Scientific Themes

Genetic alterations associated with drug resistance in agressive forms of CLL and Waldenstrom's Macroglobulinemia

Analysis of the mutational and cytogenetic abnormalities and their functional consequences in aggressive forms of chronic lymphocytic leukemia and Waldenström’s Macroglobulinemia to identify key deregulated genes as new targets for therapies.

Metabolic specificities in chronic lymphocytic leukemia: towards the design of a new therapeutic approach

Innovative approach combining bioinformatics, proteomic, ex vivo and in vivo studies to better understand the chronic lymphocytic leukemia (CLL) metabolism and to open new therapeutic avenues.

The immune repertoire of B-cell malignancies

Understanding the role of the B-cell receptor (BCR) in the development of B-cell malignancies and how antigen selection shapes their repertoire.

New therapeutic approaches for mastocytosis

Finding new drugs targeting neoplastic mast cells (MC) in systemic mastocytosis by focusing on signaling pathways deregulated in these cells.

Intraocular and cerebral lymphomas

As active members of the French oculo-cerebral lymphoma (LOC) network, our fields of expertise also include the diagnostic work-up of central nervous system lymphomas, which are very rare diseases with a pejorative prognosis.

Main publications

Krzisch D, Guedes N, Boccon-Gibod C, Baron M, Bravetti C, Davi F, Armand M, Smagghe L, Caron J, Bernard OA, Susin S, Chapiro E, Leblond V, Nguyen-Khac F, Roos-Weil D. Cytogenetic and molecular abnormalities in Waldenström’s macroglobulinemia patients: Correlations and prognostic impact. Am J Hematol. 2021 Dec 1;96(12):1569-1579

Belhouachi N, Xochelli A, Boudjoghra M, Lesty C, Cassoux N, Fardeau C, Tran THC, Choquet S, Sarker B, Houillier C, Alentorn A, LeHoang P, Soussain C, Touitou V, Merle-Beral H, Hoang-Xuan K, Bodaghi B, Stamatopoulos K, Davi F. Primary vitreoretinal lymphomas display a remarkably restricted immunoglobulin gene repertoire. Blood Adv. 2020 Apr 14;4(7):1357-1366.

Chapiro E, Pramil E, Diop M, Roos-Weil D, Dillard C, Gabillaud C, Maloum K, Settegrana C, Baseggio L, Lesesve JF, Yon M, Jondreville L, Lesty C, Davi F, Le Garff-Tavernier M, Droin N, Dessen P, Algrin C, Leblond V, Gabarre J, Bouzy S, Eclache V, Gaillard B, Callet-Bauchu E, Muller M, Lefebvre C, Nadal N, Ittel A, Struski S, Collonge-Rame MA, Quilichini B, Fert-Ferrer S, Auger N, Radford-Weiss I, Wagner L, Scheinost S, Zenz T, Susin SA, Bernard OA, Nguyen-Khac F. Genetic Characterization of B-cell Prolymphocytic Leukemia: A Prognostic Model Involving MYC and TP53. Blood. 2019 Nov 21;134(21):1821-1831

Pramil E, Herbi L, Denèfle T, Nemati F, Xiao M, Lardé E, Maloum K, Roos-Weil D, Chapiro E, Le Garff-Tavernier M, Davi F, Decaudin D, Sarfati M, Nguyen-Khac F, Merle-Béral H, Karoyan P, and Susin SA. Targeting chronic lymphocytic leukemia with N-methylated thrombospondin-1-derived peptides overcomes drug resistance. Blood Adv. 2019, 3(20):2920-2933.

Roos-Weil D, Decaudin C, Armand M, Della-Valle V, Diop MK, Ghamlouch H, Ropars V, Hérate C, Lara D, Durot E, Haddad R, Mylonas E, Damm F, Pflumio F, Stoilova B, Metzner M, Elemento O, Dessen P, Camara-Clayette V, Cosset FL, Verhoeyen E, Leblond V, Ribrag V, Cornillet-Lefebvre P, Rameau P, Azar N, Charlotte F, Morel P, Charbonnier JB, Vyas P, Mercher T, Aoufouchi S, Droin N, Guillouf C, Nguyen-Khac F*, Bernard OA*. A Recurrent Activating Missense Mutation in Waldenström Macroglobulinemia Affects the DNA Binding of the ETS Transcription Factor SPI1 and Enhances Proliferation. Cancer Discov. 2019, 9(6):796-811. * Senior co-authors.

 

All publications

Fundings