Drug resistance in hematological malignancies (DRIHM)
Director :
Santos A. Susin
Deputy Director :
Florence Nguyen-Khac
Since its creation at Cordeliers, the team has built its basic and translational research activities with the aim of improving the knowledge of the physiopathology of hematological cancers, like chronic lymphocytic leukemia (CLL), Waldenström’s macroglobulinemia (WM), B-cell prolymphocytic leukemia (B-PLL), or intraocular and cerebral lymphomas (OCL) and by translating this knowledge into the development of efficient therapies.
The main assets of the team will remain the diversity of the researchers/clinicians, the scientific reputation of the team members (involved in a wide range of national and international associations in Hematology) and the expertise in specific advanced technologies. This includes a series of cutting-edge approaches in the area of metabolism, single-cell sequencing, spatial genomic and transcriptomic, or tumor microenvironment.
To do so, we take advantage of our location on two major research/clinical sites (Cordeliers and the Pitié-Salpêtrière Hospital) where, on the one hand, we have access to high-tech core facilities and, on the other hand, we regularly obtain primary cells from patients suffering from the hematological disorders studied.
With this in mind, the team’s scientific projects are organized around 3 main axes: CLL, WM and OCL.
Key Words: Chronic Lymphocytic Leukemia; Metabolism; B-cell receptor; Drug resistance; genomic abnormalities; Intraocular and cerebral lymphomas; Waldenström’s macroglobulinemia
Scientific Themes
Chronic lymphocytic leukemia (CLL)
Chronic lymphocytic leukemia (CLL), the most common form of chronic leukemia in Western countries, is characterized by clonal proliferation and the accumulation of mature CD5+CD23+ B lymphocytes in the bone marrow, peripheral blood and lymphoid tissues.
Waldenström macroglobulinemia (WM)
Waldenstrom's macroglobulinemia (WM) is a lymphoplasmacytic lymphoma characterized by small malignant lymphocytes, plasmacytoid lymphocytes, and/or plasma cells that primarily invade the bone marrow and secrete a monoclonal immunoglobulin M (IgM).
Primary oculocerebral lymphomas
Primary central nervous system lymphoma (PCNSL) is a rare and severe form of diffuse large-cell B lymphoma, confined to the brain, spinal cord and meninges, often with ocular involvement but without peripheral extension.
Main publications
ACOX1-mediated peroxisomal fatty acid oxidation contributes to metabolic reprogramming and survival in chronic lymphocytic leukemia. Tannoury M, Ayoub M, Dehgane L, Nemazanyy I, Dubois K, Izabelle C, Brousse A, Roos-Weil D, Maloum K, Merle-Béral H, Bauvois B, Saubamea B, Chapiro E, Nguyen-Khac F, Garnier D, Susin SA. Leukemia. 2024 Feb;38(2):302-317. Link
Post-transplantation Burkitt lymphoma: a retrospective study of 55 patients. Walczak P, Choquet S, Dantal J, Boutboul D, Suarez F, Baron M, Morel V, Cluzeau T, Touati M, Elias M, Bachy E, Nicolas-Virelizier E, Houot R, Venton G, Jacquet C, Moles-Moreau MP, Jardin F, Durot E, Balegroune N, Ecotiere L, Guieze R, Kamar N, Ysebaert L, Couzi L, Gonzalez H, Roulin L, Ou K, Caillard S, Zimmermann H, Trappe RU, Roos-Weil D. Haematologica. 2023 Oct 1;108(10):2814-2819. Link
del(8p) and TNFRSF10B loss are associated with a poor prognosis and resistance to fludarabine in chronic lymphocytic leukemia. Jondreville L, Dehgane L, Doualle C, Smagghe L, Grange B, Davi F, Lerner LK, Garnier D, Bravetti C, Tournilhac O, Roos-Weil D, Boubaya M, Chapiro E, Susin SA, Nguyen-Khac F. Leukemia. 2023 Sep 26. doi: 10.1038/s41375-023-02035-3. Epub ahead of print. Link
Exploring the genetic landscape of HCV-related B-cell lymphomas using whole exome sequencing. Armand M, Degaud M, Tesson B, Laurent C, Vavasseur M, Parisot M, Hoareau-Coudert B, Canioni D, Michot JM, Charlotte F, Meignin V, Laurent C, Traverse-Gléhen A, Damotte D, Bachy E, Besson C, Hermine O, Davi F, Couronné L. Leukemia. 2023 Jun;37(6):1388-1391. Link
Extracellular Vesicles in Chronic Lymphocytic Leukemia: Tumor Microenvironment Messengers as a Basis for New Targeted Therapies? Dubois K, Tannoury M, Bauvois B, Susin SA, Garnier D. Cancers (Basel). 2023 Apr 14;15(8):2307. Link
Prevalence of IGLV3-21R110 among familial CLL: a retrospective study of 45 cases. Armand M, Verrier P, Theves F, Bravetti C, Le Garff-Tavernier M, Choquet S, Davi F. Blood Adv. 2022 Jun 28;6(12):3632-3635. Link
Cytogenetic and molecular abnormalities in Waldenström’s macroglobulinemia patients: Correlations and prognostic impact. 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. Am J Hematol. 2021 Dec 1;96(12):1569-1579. Link
Primary vitreoretinal lymphomas display a remarkably restricted immunoglobulin gene repertoire. 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. Blood Adv. 2020 Apr 14;4(7):1357-1366. Link
CANOMAD: a neurological monoclonal gammopathy of clinical significance that benefits from B-cell-targeted therapies. Le Cann M, Bouhour F, Viala K, Simon L, Tard C, Rossi C, Morel G, Lagrange E, Magy L, Créange A, Michaud M, Franques J, Echaniz-Laguna A, Antoine JC, Baron M, Arnulf B, Puma A, Delmont E, Maisonobe T, Leblond V, Roos-Weil D.Blood. 2020 Nov 19;136(21):2428-2436. Link
Genetic Characterization of B-cell Prolymphocytic Leukemia: A Prognostic Model Involving MYC and TP53. 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. Blood. 2019 Nov 21;134(21):1821-1831. Link
Targeting chronic lymphocytic leukemia with N-methylated thrombospondin-1-derived peptides overcomes drug resistance. 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. Blood Adv. 2019, 3(20):2920-2933. Link
A Recurrent Activating Missense Mutation in Waldenström Macroglobulinemia Affects the DNA Binding of the ETS Transcription Factor SPI1 and Enhances Proliferation. 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*. Cancer Discov. 2019, 9(6):796-811. * Senior co-authors. Link
All publications
