Effect of tyrosine kinase inhibition using imatinib on normal lymphohematopoietic cells.
Imatinib is a selective tyrosine kinase inhibitor used for the treatment of Philadelphia chromosome-positive leukemias and other malignancies. An important clinical observation is that imatinib can affect the function of normal nonmalignant cells resulting in myelosuppression in treated patients. This observation is supported by the recent findings suggesting that imatinib might affect mobilization, proliferation, and differentiation of hematopoietic progenitor cells while leaving hematopoietic stem cells unaffected. Furthermore, the induction of a specific T cell response seems to be impaired in chronic myeloid leukemia (CML) patients treated with imatinib in contrast to patients receiving interferon-alpha. Recent studies demonstrate that in vitro exposure of mobilized human CD34(+) progenitors to imatinib inhibits their differentiation into dendritic cells. This is of importance as some of the therapeutic effects in the treatment of patients with CML are mediated by the induction of leukemia-specific T cell responses. Studies investigating the effects of imatinib on normal hematopoiesis are of interest because they might help us better understand the side effects observed clinically and might lead to the identification of novel therapeutic applications of the drug (e.g., in Bcr-Abl(-) myeloproliferative disorders and potentially as an immunomodulatory agent).
Balabanov
Stefan
S
Klinik für Onkologie, Hämatologie und KMT, Zentrum für Innere Medizin, Universitäts-Klinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Appel
Silke
S
Kanz
Lothar
L
Brossart
Peter
P
Brümmendorf
Tim H
TH
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D003713:Dendritic Cells / Q000187:drug effects; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D000068877:Imatinib Mesylate; D008954:Models, Biological; D010879:Piperazines / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl