Reference : Despite inhibition of hematopoietic progenitor cell growth in vitro, the tyrosine kin...
Scientific journals : Article
Human health sciences : Hematology
http://hdl.handle.net/2268/6956
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.
English
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 - ULg > Département des sciences cliniques > Hématologie - Oncologie médicale >]
Greimers, Roland [Centre Hospitalier Universitaire de Liège - CHU > > Anatomie pathologique >]
Di Stefano, Ivano [> > > >]
Gothot, André mailto [Centre Hospitalier Universitaire de Liège - CHU > > Hématologie biologique et immuno hématologie >]
Beguin, Yves [Centre Hospitalier Universitaire de Liège - CHU > > Hématologie clinique >]
2006
Stem Cells
AlphaMed Company, Inc.
24
7
1814-21
Yes (verified by ORBi)
International
1066-5099
1549-4918
Miamisburg
OH
[en] Animals ; Antigens, CD/metabolism ; Apoptosis/drug effects ; Blood Cells/drug effects ; Cell Adhesion/drug effects ; Cell Cycle/drug effects ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cells, Cultured ; Fetal Blood/drug effects ; Fibronectins/metabolism ; Glycoproteins/metabolism ; Graft vs Leukemia Effect/drug effects ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/drug effects ; Humans ; Integrin alpha4beta1/metabolism ; Integrin alpha5beta1/metabolism ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/prevention & control ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Peptides/metabolism ; Piperazines/pharmacology ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins c-kit/physiology ; Pyrimidines/pharmacology ; Receptors, CXCR4/metabolism ; Receptors, Platelet-Derived Growth Factor/metabolism ; Xenograft Model Antitumor Assays
[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.
http://hdl.handle.net/2268/6956
10.1634/stemcells.2005-0290
A. Gothot and Y. Beguin contributed equally to this work

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