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
Autor: | Ivano Di Stefano, André Gothot, Nathalie Meuris, Yves Beguin, Emilie Castermans, Olivier Giet, Laurence Pirson, Roland Greimers, Frédéric Baron |
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Rok vydání: | 2006 |
Předmět: |
medicine.medical_treatment
Stem cell factor Apoptosis Hematopoietic stem cell transplantation Mice SCID Pharmacology Integrin alpha4beta1 CXCR4 Piperazines Mice Cell Movement Mice Inbred NOD hemic and lymphatic diseases Receptors Platelet-Derived Growth Factor AC133 Antigen Cells Cultured Cell Cycle Hematopoietic Stem Cell Transplantation Hematopoietic stem cell Fetal Blood Proto-Oncogene Proteins c-kit medicine.anatomical_structure Benzamides Imatinib Mesylate Molecular Medicine medicine.drug Integrin alpha5beta1 Receptors CXCR4 Graft vs Leukemia Effect Biology Antigens CD Leukemia Myelogenous Chronic BCR-ABL Positive medicine Cell Adhesion Animals Humans Progenitor cell neoplasms Protein Kinase Inhibitors Cell Proliferation Glycoproteins Blood Cells Imatinib Cell Biology Hematopoietic Stem Cells Xenograft Model Antitumor Assays Fibronectins Imatinib mesylate Pyrimidines Cancer research Bone marrow Peptides Developmental Biology |
Zdroj: | Stem cells (Dayton, Ohio). 24(7) |
ISSN: | 1066-5099 |
Popis: | 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. |
Databáze: | OpenAIRE |
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