Epigenetics, epidemiology and personalized treatment of hematological malignancies: Epi2THM

The team has 3 interconnecting research themes that are globally aimed at innovation in the personalised prevention, diagnosis/prognosis and treatment of blood cancers with focus on leukemia and B cell lymphoma.

1- elucidate new (epi)genetic disease mechanisms of interest as predictive risk factors or for therapeutic targeting in leukemia and lymphoma, through high throughput (epi)genomic screens in model cellular systems and functional analyses (CRISPR-Cas9) in mouse and human systems, together with clinical validation by analyses in patient samples (curated by the team or in the setting of multicentre clinical trials)

2- identify, by epidemiology approaches in population-based data, factors that influence survival, access to and impact of treatment innovation and quality of life in blood cancer patients

3- to leverage our findings concerning patient (epidemiology and clinical) and disease characteristics [(epi)genetic], together with new residual disease diagnostic approaches (Cf DNA and imaging), for dynamic prediction of patient outcomes by precision medicine approaches.

Selected publications

Repeat element activation-driven inflammation; role of NFKB and implications in normal development and cancer? Dumétier B, Sauter C, Hajmirza A, Pernon B, Aucagne R, Fournier C, Row C, Guidez F, Rossi C, Lepage C, Delva L, Callanan MB. Biomedicines, Review 2022, in press

Protein Arginine Methyltransferases as Therapeutic Targets in Hematological Malignancies. Sauter C, Simonet J, Guidez F, Dumétier B, Pernon B, Callanan M, Bastie JN, Aucagne R, Delva L. Cancers (Basel), Review 2022, PMID: 36358861

Ibrutinib, obinutuzumab, and venetoclax in relapsed and untreated patients with mantle cell lymphoma: a phase 1/2 trial. Le Gouill S, Morschhauser F, Chiron D, Bouabdallah K, Cartron G, Casasnovas O, Bodet-Milin C, Ragot S, Bossard C, Nadal N, Herbaux C, Tessoulin B, Tchernonog E, Rossi C, McCulloch R, Gastinne T, Callanan MB*, Rule S*. Blood, 2021, PMID: 33181832 *equal contribution

Identification of novel, clonally stable, somatic mutations targeting transcription factors PAX5 and NKX2-3, the epigenetic regulator LRIF1, and BRAF in a case of atypical B-cell chronic lymphocytic leukemia harboring a t(14;18)(q32;q21). Burlet B, Ramla S, Fournier C, Abrey-Recalde MJ, Sauter C, Chrétien ML, Rossi C, Duffourd Y, Ragot S, Buriller C, Tournier B, Chapusot C, Nadal N, Racine J, Guy J, Bailly F, Martin L, Casasnovas O, Bastie JN, Caillot D, Albuisson J, Broccardo C, Thieblemont C, Delva L, Maynadié M, Aucagne R*, Callanan MB*. Cold Spring Harb Mol Case Stud, 2021, PMID: 33608382 *co-corresponding authors

PLZF Acetylation Levels Regulate NKT Cell Differentiation. Klibi J, Joseph C, Delord M, Teissandier A, Lucas B, Chomienne C, Toubert A, Bourc'his D, Guidez F*, Benlagha K*. J Immunol, 2021, PMID: 34282003 *co-last, co-corresponding authors

Flexible Modeling of Net Survival and Cure by AML Subtype and Age: A French Population-Based Study from FRANCIM. Mounier M*, Romain G, Callanan M, Alla AD, Boussari O, Maynadié M, Colonna M, Jooste V. J Clin Med, 2021, PMID: 33924506 *Corresponding author.

High-fat diet intensifies MLL-AF9-induced acute myeloid leukemia through activation of the FLT3 signaling in mouse primitive hematopoietic cells. Hermetet F, Mshaik R, Simonet J, Callier P, Delva L, Quéré R. Sci Rep, 2020, PMID: 32999332.

High-fat diet disturbs lipid raft/TGF-β signaling-mediated maintenance of hematopoietic stem cells in mouse bone marrow. Hermetet F, Buffière A, Aznague A, Pais de Barros JP, Bastie JN, Delva L, Quéré R. Nat Commun, 2019, PMID: 30705272

A phase 2 study of rituximab, bendamustine, bortezomib and dexamethasone for first-line treatment of older patients with mantle cell lymphoma. Gressin R, Daguindau N, Tempescul A, Moreau A, Carras S, Tchernonog E, Schmitt A, Houot R, Dartigeas C, Pignon JM, Corm S, Banos A, Mounier C, Dupuis J, Macro M, Fleury J, Jardin F, Sarkozy C, Damaj G, Feugier P, Fornecker LM, Chabrot C, Dorvaux V, Bouadallah K, Amorin S, Garidi R, Voillat L, Joly B, Celigny PS, Morineau N, Moles MP, Zerazhi H, Fontan J, Arkam Y, Alexis M, Delwail V, Vilque JP, Ysebaert L, Le Gouill S, Callanan MB; Lymphoma Study Association. Haematologica, 2019, PMID: 30171024

PET-adapted treatment for newly diagnosed advanced Hodgkin lymphoma (AHL2011): a randomised, multicentre, non-inferiority, phase 3 study. Casasnovas RO, Bouabdallah R, Brice P, Lazarovici J, Ghesquieres H, Stamatoullas A, Dupuis J, Gac AC, Gastinne T, Joly B, Bouabdallah K, Nicolas-Virelizier E, Feugier P, Morschhauser F, Delarue R, Farhat H, Quittet P, Berriolo-Riedinger A, Tempescul A, Edeline V, Maisonneuve H, Fornecker LM, Lamy T, Delmer A, Dartigues P, Martin L, André M, Mounier N, Traverse-Glehen A, Meignan M. Lancet Oncol, 2019, PMID: 30658935

The Need for a Consensus Next-generation Sequencing Panel for Mature Lymphoid Malignancies. Sujobert P, Le Bris Y, de Leval L, Gros A, Merlio JP, Pastoret C, Huet S, Sarkozy C, Davi F, Callanan M, Thieblemont C, Sibon D, Asnafi V, Preudhomme C, Gaulard P, Jardin F, Salles G, Macintyre E. Hemasphere, 2018, PMID: 31723808

Haploinsufficiency for NR3C1, the gene encoding the glucocorticoid receptor, in blastic plasmacytoid dendritic cell neoplasms. Emadali A, Hoghoughi N, Duley S, Hajmirza A, Verhoeyen E, Cosset FL, Bertrand P, Roumier C, Roggy A, Suchaud-Martin C, Chauvet M, Bertrand S, Hamaidia S, Rousseaux S, Josserand V, Charles J, Templier I, Maeda T, Bruder-Costa J, Chaperot L, Plumas J, Jacob MC, Bonnefoix T, Park S, Gressin R, Tensen CP, Mecucci C, Macintyre E, Leroux D, Brambilla E, Nguyen-Khac F, Luquet I, Penther D, Bastard C, Jardin F, Lefebvre C, Garnache F, Callanan MB. Blood, 2016, PMID: 27060168