Normal and Leukemic hematopoietic stem cells: autorenewal, signaling and targets

Research themes

The INSERM team “Normal and Leukemic Hematopoietic Stem Cells: Self-renewal, Signaling and Therapeutic Targets” was born from the desire to establish an ambitious research by bringing together several researchers and physicians wishing to develop basic and translational research. This team brings together the group of Dr. Zoran Ivanovic from the French Blood Institute – Aquitaine-Limousin, the group of Dr. Jean-Max Pasquet of the INSERM 1035 unit team oncogenic tyrosine kinase signaling and the Department of Professor Noel Milpied, Head of the Department of Clinical Hematology And cell therapy. The development of targeted therapies has greatly improved the treatment and fate of patients as well as the discovery of new signaling pathways to improve not only the management of patients but also our knowledge of leukemogenesis. The main challenges today are to characterize normal stem cells for transplantation, to improve their conservation and expansion, and to study leukemic stem cells and their microenvironment to identify mechanisms in the haematopoietic niche that control Resistance to current therapeutics. This research, conducted in close collaboration with the clinical hematology department, will enable us to translate our expertise into the therapeutic management of acute leukemia.

Publications

1. GIOIA R, LEROY C, DRULLION C, LAGARDE V, ETIENNE G, DULUCQ S, LIPPERT E, ROCHE S, MAHON F, PASQUET JM. Quantitative phosphoproteomics revealed interplay between Syk and Lyn in the resistance to nilotinib in chronic myeloid leukemia cells. Blood. 2011 ; 118(8) : 2211-2221.
2. GUITART AV, DEBEISSAT C, HERMITTE F, VILLACRECES A, IVANOVIC Z, BOEUF H, PRALORAN V. Very low oxygen concentration (0.1%) reveals two FDCP-Mix cell subpopulations that differ by their cell cycling, differentiation and p27(KIP1) expression. Cell Death Differ, 18:174-82. 2011.
3. HAMMOUD M, VLASKI M, DUCHEZ P, CHEVALEYRE J, LAFARGE X, BOIRON J-M, BRUNET DE LA GRANGE P, IVANOVIC Z. Combination of low O2 concentration and mesenchymal stromal cells during culture of cord blood CD34+ cells improves the maintenance and proliferative capacity of hematopoietic stem cells. J Cell Physiol, 227:2750-8, 2012.
4. RIVALAIN N, ROQUAIN J, BOIRON JM, MAUREL JP, LARGETEAU A, IVANOVIC Z, DEMAZEAU G. High hydrostatic pressure treatment for the inactivation of Staphylococcus aureus in human blood plasma. N Biotechnol 29:409-14, 2012.
5. DUCHEZ P, CHEVALEYRE J, VLASKI M, DAZEY B, MILPIED N, BOIRON J-M, IVANOVIC Z. Definitive set-up of clinical-scale procedure for ex-vivo expansion of cord blood hematopoietic cells for transplantation. Cell Transplant, 21: 2517–21, 2012.
6. DRULLION C, LAGARDE V, GIOIA R, LEGEMBRE P, PRIAULT M, CARDINAUD B, LIPPERT E, MAHON FX, PASQUET JM. Mycophenolic acid overcomes imatinib and nilotinib resistance of chronic myeloid leukemia cells by apoptosis or a senescent-like cell cycle arrest. Leuk.Res.Treat. 2012; 861301, 9.
7. DRULLION C, TREGOAT C, LAGARDE V, TAN S, GIOIA R, PRIAULT M, DJAVAHERI-MERGNY M, BRISSON A, AUBERGER P, MAHON FX, PASQUET JM. Apoptosis and autophagy play opposite roles on Imatinib-induced K562 leukemia cells senescence. Cell Death and Dis. 2012 ; 2012 Aug 16;3:e373.
8. BEDEL A, PASQUET JM, LIPPERT E, TAILLEPIERRE M, LAGARDE V, DABERNAT S, DUBUS P, CHARAF L, BELIVEAU F, DE VERNEUIL H, RICHARD E, MAHON FX, MOREAU-GAUDRY F. Variable Behavior of iPSCs Derived from CML Patients for Response to TKI and Hematopoietic Differentiation. PLoS One. 2013 Aug 23;8(8):e71596.
9. JAUSSAUD J, BIAIS M, CALDERON J, CHEVALEYRE J, DUCHEZ P, IVANOVIC Z, COUFFINHAL T, BARANDON L. Hypoxia-preconditioned mesenchymal stromal cells improve cardiac function in a swine model of chronic myocardial ischaemia. Eur J Cardiothorac Surg 43:1050-7, 2013.
10. DUCHEZ P, CHEVALEYRE J, BRUNET DE LA GRANGE P, VLASKI M, BOIRON JM, IVANOVIC Z. Functional stability (at +4°c) of hematopoietic stem and progenitor cells amplified ex vivo from cord blood CD34+ cells. Cell Transplant, 22 : 1501–06, 2013.
11. BRUNET DE LA GRANGE P, VLASKI M, DUCHEZ P, CHEVALEYRE J, LAPOSTOLLE V, BOIRON J-M, PRALORAN V, IVANOVIC Z. Long-term repopulating hematopoietic stem cells and “side population” in human steady state peripheral blood. Stem Cell Res 11:625-33, 2013.
12. CHEVALEYRE J, DUCHEZ P, RODRIGUEZ L, VLASKI M, VILLACRECES A, CONRAD-LAPOSTOLLE V, PRALORAN V, IVANOVIC Z, BRUNET DE LA GRANGE P. Busulfan administration flexibility increases the applicability of Scid Repopulating Cell Assay in NSG mouse model. PLoS One, 17; 8(9): e74361, 2013.
13. LECONET W, LARBOURET C, CHARDÈS T, THOMAS G, NEIVEYANS M, BUSSON M, JARLIER M, RADOSEVIC-ROBIN N, PUGNIÈRE M, BERNEX F, PENAULT-LLORCA F, PASQUET JM, PÈLEGRIN A, ROBERT B. Preclinical validation of AXL receptor as a target for antibody-based pancreatic cancer immunotherapy. Oncogene. 2013 Nov 18.
14. GIOIA R, TREGOAT C, DUMAS PY, LAGARDE V, PROUZET-MAULEON V, DESPLAT V, SIRVENT A, PRALORAN V, LIPPERT E, VILLACRECES A, LECONET W, ROBERT B, VIGON I, ROCHE S, MAHON FX, PASQUET JM. CBL controls a tyrosine kinase network involving AXL, SYK and LYN in nilotinib-resistant chronic myeloid leukemia. J Pathol. 2015 Sep;237(1):14-24.
15. LAGARDE V, MAHON FX, PASQUET JM. Loss of SYK and LYN tyrosine kinase expression impair ponatinib-induced apoptosis in K562 cells. J.Trans.Prot.Res. 2015.
16. IANNICIELLO A, DRULLION C, DUMAS PY, VILLACRECES A, PEYTOUR P, CHEVALEYRE J, BRUNET DE LA GRANGE P, VIGON I, DESPLAT V, GUITART A, PRIAULT M, DELLO SBARBA P, IVANOVIC Z, MAHON FXAND PASQUET JM. Chronic myeloid leukemia progenitor cells require autophagy when leaving hypoxia-induced quiescence. Oncotarget. 2017. In revision.

Composition de l'équipe

M AVALON, Tech; F BIJOU, PH; P BRUNET DE LA GRANGE, MRech; S CASTEDE, ATER; L RODRIGUEZ IR; V DESPLAT, MCU; S DIMICOLI, PH; P DUCHEZ, IR; PY DUMAS, Doc; V LABAT, IR; X LAFARGE, PH; V LAPOSTOLLE, MCU; T LEGUAY, PH; D LONCARIC, Doc; N MILPIED, PU-PH; A PIGNEUX, PU-PH; V PRALORAN, PU-PH; R TABRIZI, PH; I VIGON, CR; S VIGOUROUX, PH; A VILLACRECES, IE; M VLASKI-LAFARGE, CE.