Despite inhibition of hematopoietic progenitor cell growth in vitro, the tyrosine kinase inhibitor imatinib does not impair engraftment of human CD133⁺ cells into NOD/SCID2m^null mice

¹ Center for Cellular and Molecular Therapy and Department of Medicine, Division of Hematology, University of Liège, Liège, Belgium
² Laboratory of Pathological Anatomy and Cytology, University of Liège, Liège, Belgium
³ Center for Cellular and Molecular Therapy and Department of Clinical Biology, Division of Laboratory Hematology, University of Liège, Liège, Belgium

^* To whom correspondence should be addressed. E-mail: Yves.Beguin{at}chu.ulg.ac.be.

	Abstract

There is a potentiel interest for combining allogeneic hematopoietic cell transplantation (HCT), and particularly allogeneic HCT with a non-myeloablative regimen, to the tyrosine kinase inhibitor imatinib (Glivec^R), in order to maximize anti-leukemic activity against Philadelphia-chromosome positive leukemias. However, as imatinib inhibits c-kit, the stem cell factor receptor, it could interfere with bone marrow engraftment. In this study, we examined the impact of imatinib on normal progenitor cell function. Imatinib decreased the colony forming capacity of mobilized peripheral blood human CD133⁺ cells but not that of long-term culture- initiating cells (LTC-IC). Imatinib also decreased the proliferation of cytokine-stimulated CD133⁺ cells, but did not induce apoptosis of these cells. Neither VLA-4, VLA-5 nor CXCR4 expression of CD133⁺ cells was modified by imatinib, but imatinib decreased the ability of CD133⁺ cells to migrate. Finally, imatinib did not decrease engraftment of CD133⁺ cells into irradiated NOD/SCID/2m^null mice conditioned with 3 Gy or 1 Gy total body irradiation. In summary, our results suggest that, despite inhibition of hematopoietic progenitor cell growth in vitro, imatinib does not interfere with hematopoietic stem cell engraftment.