Cell and molecule mechanisms of haematological disorders and therapeutic implications

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Research topics & objectives

The team is interested in various physio-pathological aspects and the treatment of benign and malignant blood diseases. The research objectives developed within the laboratory are: i) the characterisation of the mechanisms implicated in the pathogenesis of benign and malignant blood diseases, ii) the development of new therapeutic strategies, iii) the development of clinical trials and iv) the transfer of new technologies.

Research topics

  • Lymphoproliferation associated with viruses (HTLV1, HCV, EBV).
  • Lymphoproliferation associated with immune deficiencies.
  • Mantle-cell lymphomas.
  • Enteropathy-associated T-cell lymphomas (EATL).
  • Sporadic forms of hemophagocytic lymphohistiocytosis.
  • GVH.
  • Anti-tumour immunotherapy.

Lymphoma sub-types

  • Lymphomas linked to HTLV1.
  • Lymphomas linked to HCV;
  • NK/T-cell lymphomas.
  • Lymphomas associated with immune deficiencies.
  • Mantle-cell lymphomas.
  • Enteropathy-associated T-cell lymphomas (EATL).

Key words

Pathogenesis models of blood diseases, Therapeutic innovation, Valorisation.

Olivier Hermine Recherche Lymphome
Olivier Hermine Manager - Créteil
MantleCellLymphoma
EXPERTISE

BIOLOGICAL TARGETS AND IN VITRO/IN VIVO/EX VIVO MODELS

Targets

  • Immune checkpoints and immunological synapses.
  • Tyrosines kinase (ex: Ckit, PDGF-R, Lyn).
  • NK receptors (ex: KIR).
  • Neuropilin 1 (NRP1).
  • Transferrin receptor (TFR).

Models

  • In vitro: cellular lineages of B and T-cell non-Hodgkin lymphomas and of acute lymphoblastic leukaemia, co-culture of lineages or stem cells from patients with macrophages or NK cells, immunological synapses.
  • In vivo: immunodeficient mice (xenografts of lineages or stem cells), spontaneous models of blood diseases in animals (cat: gastrointestinal lymphomas with small T cells).
  • Ex vivo: in vitro expansion of iNKT cells from patients, expansion of normal and pathological CD34+ cells.

BLOOD AND TISSUE BIOMARKERS

  • Proliferation capacity of iNKT cells after expansion in vitro as a predictive marker of GVHD.
  • Development of prognostic biomarkers: the expression of NRP1 and TFR as prognostic factors.

EARLY ACTIVITY PHARMACODYNAMIC SIGNALS

  • Kinases activation.
  • Telomeres and telomerase activity.

TOOLS, PROCESSES AND PLATFORMS LINKED TO THE CLINICAL RESEARCH

  • Bioinformatics platforms (sequencing data analysis) and biostatistics.
  • Various imaging techniques (Image stream, confocal microscopy).
  • Patient cohorts: EATL, HTLV1-associated lymphomas, NK/T-cell lymphomas, gamma/delta panniculitis, mantle-cell lymphomas.

INNOVATING TECHNOLOGY

  • NGS (exome, RNA seq).
  • CRISPR-CAS9.
  • ADCC study.
  • Apoptosis study.
  • Study of the vaccine response in mouse models in vivo.
  • Study of the regulatory activity of regulating T lymphocytes.
  • Study of lymphocytotoxicity (mediated by T CD8+ lymphocytes or NK cells).

Platforms & technical resources

Platforms available at the Imagine Institute:

  • Genomics (exome sequencing, targeted resequencing, SNP array, RNAseq).
  • Microscopy (confocal microscopy, Image stream, video microscope).
  • Proteomics.
  • Animal studies / transgenesis.
  • Bioinformatics platforms (sequencing data analysis) and biostatistics.

R&D offer

  • Collaborative and contractual research: pharmacological modulation of biological targets, development of prognostic biomarkers.
  • Expertise: HTLV1-associated lymphomas, mantle-cell lymphomas, lymphomas associated with immune deficiencies, HCV-associated lymphomas.
  • Clinical databases: HTLV1-associated lymphomas, EATL, NK/T-cell lymphomas.
  • Collections of tumour samples: EATL, HTLV1-associated lymphomas, NK/T-cell lymphomas, gamma/delta panniculitis.
  • Spontaneous animal tumour models.

Top 5 of recent publications:

Calym CELAC network. NKp46 is adiagnostic biomarker and may be a therapeutic target in gastrointestinal T-celllymphoproliferative diseases: a CELAC study.
Cheminant M, Bruneau J, Malamut G, Sibon D, Guegan N, van Gils T, Cording S, Trinquand A, Verkarre V, Lhermitte L, Brousse N, Jannot AS, Khater S, Frenzel L, Delarue R, Suarez F, Marçais A, Mulder CJ, Macintyre E, Asnafi V, Pouyet L, Bonnafous C, Lhospice F, Molina TJ, Meresse B, Cellier C, Cerf-Bensussan N, Hermine O.
Gut.2019;68:1396–405. Learn more
Calym Enhanced Renewal of Erythroid Progenitors inMyelodysplastic Anemia by Peripheral Serotonin
Sibon D, Coman T, Rossignol J, Lamarque M, Kosmider O, Bayard E, Fouquet G, Rignault R, Topçu S, Bonneau P, Bernex F, Dussiot M, Deroy K, Laurent L, Callebert J, Launay JM, Georgin-Lavialle S, Courtois G, Maroteaux L, Vaillancourt C, Fontenay M, Hermine O, Côté F.
Cell Rep.2019;26:3246-3256.e4. Learn more
Calym LYSA Group. Rituximab after Autologous Stem-Cell Transplantation in Mantle-Cell Lymphoma.N Engl J Med.
Le Gouill S, Thieblemont C, Oberic L, Moreau A, Bouabdallah K, Dartigeas C, Damaj G, Gastinne T, Ribrag V, Feugier P, Casasnovas O, Zerazhi H, Haioun C, Maisonneuve H, Houot R, Jardin F, Van Den Neste E, Tournilhac O, Le Dû K, Morschhauser F, Cartron G, Fornecker LM, Canioni D, Callanan M, Béné MC, Salles G, Tilly H, Lamy T, Gressin R, Hermine O.
2017;377:1250-1260 Learn more
Calym European Mantle Cell Lymphoma Network. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network.
Hermine O, Hoster E, Walewski J, Bosly A, Stilgenbauer S, Thieblemont C, Szymczyk M, Bouabdallah R, Kneba M, Hallek M, Salles G, Feugier P, Ribrag V, Birkmann J, Forstpointner R, Haioun C, Hänel M, Casasnovas RO, Finke J, Peter N, Bouabdallah K, Sebban C, Fischer T, Dührsen U, Metzner B, Maschmeyer G, Kanz L, Schmidt C, Delarue R, Brousse N, Klapper W, Macintyre E, Delfau-Larue MH, Pott C, Hiddemann W, Unterhalt M, Dreyling M.
Lancet. 2016;388:565-75. Learn more
Calym G-CSFmobilizes CD34+ regulatory monocytes that inhibit graft-versus-host disease. Sci.Transl.
D'Aveni M, Rossignol J, Coman T, Sivakumaran S, Henderson S, Manzo T, Santos e Sousa P, Bruneau J, Fouquet G, Zavala F, Alegria-Prévot O, Garfa-Traoré M, Suarez F, Trebeden-Nègre H, Mohty M, Bennett CL, Chakraverty R, Hermine O, Rubio MT.
Med. 2015;7:281ra42. Learn more