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
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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