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TRANSLATIONAL AND CLINICAL RESEARCH

Despite Inhibition of Hematopoietic Progenitor Cell Growth In Vitro, the Tyrosine Kinase Inhibitor Imatinib Does Not Impair Engraftment of Human CD133⁺ Cells into NOD/SCIDß2m^Null Mice

^aCenter for Cellular and Molecular Therapy, University of Liège, Liège, Belgium;
^bDepartment of Medicine, Division of Hematology, University of Liège, Liège, Belgium;
^cLaboratory of Pathological Anatomy and Cytology, University of Liège, Liège, Belgium;
^dDepartment of Clinical Biology, Division of Laboratory Hematology, University of Liège, Liège, Belgium

Key Words. Allogeneic stem cell transplantation • Chronic myeloid leukemia • Imatinib

Correspondence: Yves Beguin, M.D.,University of Liège, Department of Hematology, CHU Sart Tilman, 4000 Liège, Belgium. Telephone: +32-4-366 72 01; Fax: +32-4-366 88 55; email: yves.beguin{at}chu.ulg.ac.be

Received on June 29, 2005; accepted for publication on March 31, 2006.

First published online in STEM CELLS EXPRESS  April 13, 2006.

There is potential interest for combining allogeneic hematopoietic cell transplantation (HCT), and particularly allogeneic HCT with a nonmyeloablative regimen, to the tyrosine kinase inhibitor imatinib (Glivec; Novartis, Basel, Switzerland, http://www.novartis.com) in order to maximize anti-leukemic activity against Philadelphia chromosome-positive leukemias. However, because 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. Imatinib also decreased the proliferation of cytokine-stimulated CD133⁺ cells but did not induce apoptosis of these cells. Expression of very late antigen (VLA)-4, VLA-5, and CXCR4 of CD133⁺ cells was not modified by imatinib, but imatinib decreased the ability of CD133⁺ cells to migrate. Finally, imatinib did not decrease engraftment of CD133⁺ cells into irradiated nonobese diabetic/severe combined immunodeficient/ß2m^null mice conditioned with 3 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.