Jean-Max Pasquet: Control of leukemia cell resistance by hematopoietic niche
Organizer: Paulo de Sepulveda
Various malignant transformations of hematopoietic stem cells can lead to leukaemia. These cells mainly reside in the bone marrow and all treatments developed to date target their proliferation or even their differentiation without completely eliminating them. Indeed, the maintenance of a pool of initiating cells resistant to all therapeutic approaches leads to relapses for which the prognosis is frequently poor. Modeling of the physicochemical parameters of the hematopoietic niche, such as mesenchymal stromal cell culture and low O2 concentrations, now makes it possible to reproduce some of these conditions in vitro, thus offering more physiological means of study, more relevant screening and selection methods.
- Hypoxia/hypercapnia-induced adaptation maintains functional capacity of cord blood stem and progenitor cells at 4°C. VLASKI M, NEGRONI L, KOVACEVIC-FILIPOVIC M, GUIBERT C, BRUNET DE LA GRANGE P, ROSSIGNOL R, CHEVALEYRE J, DUCHEZ P, LAFARGE X, PRALORAN V, SCHMITTER JM, IVANOVIC Z. J Cell Physiol. 2014 Dec;229(12):2153-65.
- CBL controls a tyrosine kinase network involving AXL, SYK and LYN in nilotinib-resistant chronic myeloid leukemia. GIOIA R, TREGOAT C, DUMAS PY, LAGARDE V, PROUZET-MAULÉON V, DESPLAT V, SIRVENT A, PRALORAN V, LIPPERT E, VILLACRECES A, LECONET W, ROBERT B, VIGON I, ROCHE S, MAHON FX, PASQUET JM. J Pathol. 2015 Sep;237(1):14-24.
- Chronic myeloid leukemia progenitor cells require autophagy when leaving hypoxia-induced quiescence. IANNICIELLO A, DRULLION C, DUMAS PY, GUITART A, VILLACRECES A, PEYTOUR P, CHEVALEYRE J, BRUNET DE LA GRANGE P, VIGON I, DESPLAT V, PRIAULT M, DELLO SBARBA P, IVANOVIC Z, MAHON FX AND PASQUET JM. Oncotarget. 2017.
- Microenvironment favors FLT3-ITD AML resistance to FLT3-TKI through hypoxia- and STAT5- dependent upregulation of AXL. DUMAS PY, NAUDIN C, MARTIN-LANNERÉE S, IZAC B, CASETTI L, MANSIER O, ROUSSEAU B, ARTUS A, DUFOSSÉE M, GIESE A, DUBUS P, PIGNEUX A, PRALORAN V, BIDET A, VILLACRECES A, GUITART A, MILPIED N, KOSMIDER O, VIGON I, DESPLAT V, DUSANTER-FOURT I AND PASQUET JM. Submitted to Blood.