Balabanov Stefan, Appel Silke, Kanz Lothar, Brossart Peter, Brümmendorf Tim H
Klinik für Onkologie, Hämatologie und KMT, Zentrum für Innere Medizin, Universitäts-Klinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Ann N Y Acad Sci. 2005 Jun;1044:168-77. doi: 10.1196/annals.1349.022.
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).
伊马替尼是一种选择性酪氨酸激酶抑制剂，用于治疗费城染色体阳性白血病和其他恶性肿瘤。一项重要的临床观察结果是，伊马替尼可影响正常非恶性细胞的功能，导致接受治疗的患者出现骨髓抑制。最近的研究结果支持了这一观察结果，这些结果表明伊马替尼可能影响造血祖细胞的动员、增殖和分化，而对造血干细胞没有影响。此外，与接受α干扰素治疗的患者相比，接受伊马替尼治疗的慢性髓性白血病（CML）患者似乎存在特异性T细胞反应诱导受损的情况。最近的研究表明，动员的人CD34(+)祖细胞在体外暴露于伊马替尼会抑制其分化为树突状细胞。这一点很重要，因为CML患者治疗中的一些治疗效果是由白血病特异性T细胞反应的诱导介导的。研究伊马替尼对正常造血的影响很有意义，因为它们可能有助于我们更好地理解临床上观察到的副作用，并可能导致发现该药物的新治疗应用（例如，在Bcr-Abl(-)骨髓增殖性疾病中，以及可能作为一种免疫调节剂）。
