Epigenetics, epidemiology and personalized treatment of hematological malignancies: Epi2THM

RGHL

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
    • Institut National de la Santé Et de la Recherche Médicale
    • Tirets de séparation
    • L'Inserm en région Grand-Est
    Support :

    Agence Nationale de la Recherche Agrosup Dijon Fondation ARC pour la recherche sur le cancer Cent Pour Sang La Vie CHU Dijon Centre Georges François LECLERC
    Conseil Régional de Bourgogne Délégation régionale à la recherche et à la technologie Institut National du Cancer ELA Association Européenne contre les leucodystrophies EPHE : Dijon - Université de Bourgogne Faculté de Médecine de Dijon
    UFR Pharmacie - uB, Dijon Fondation de France Fondation pour la Recherche Médicale en France Laboratoire d’excellence - LipSTIC Dijon La Ligue Contre le Cancer Société française d'hématologie