Despite inhibition of hematopoietic progenitor cell growth in vitro, the tyrosine kinase inhibitor imatinib does not impair engraftment of human CD133+ cells into NOD/SCIDbeta2mNull mice.
[en] 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/beta2m(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.
Disciplines :
Hematology
Author, co-author :
Pirson, Laurence ✱; Centre Hospitalier Universitaire de Liège - CHU > Toxicologie clinique
Baron, Frédéric ✱; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Meuris, Nathalie ; Centre Hospitalier Universitaire de Liège - CHU > Génétique
Giet, Olivier ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Castermans, Emilie ; Université de Liège - ULiège > Département des sciences cliniques > Hématologie - Oncologie médicale
Greimers, Roland ; Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
Di Stefano, Ivano
Gothot, André ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie biologique et immuno hématologie
Beguin, Yves ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
✱ These authors have contributed equally to this work.
Language :
English
Title :
Despite inhibition of hematopoietic progenitor cell growth in vitro, the tyrosine kinase inhibitor imatinib does not impair engraftment of human CD133+ cells into NOD/SCIDbeta2mNull mice.
Publication date :
2006
Journal title :
Stem Cells
ISSN :
1066-5099
eISSN :
1549-4918
Publisher :
AlphaMed Company, Inc., Miamisburg, United States - Ohio
Volume :
24
Issue :
7
Pages :
1814-21
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
A. Gothot and Y. Beguin contributed equally to this work
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