摘要
临床数据显示,甲磺酸伊马替尼在治疗慢性髓系白血病(CML)过程中出现血小板降低等副反应,因此考虑将伊马替尼应用于血小板增多症及其他骨髓增殖性疾病(MPD)。研究证实,伊马替尼不仅可以抑制BCR/ABL突变基因,对其他酪氨酸激酶受体基因如PDGFR、JAK2V617F及C-KIT突变同样也有抑制作用,从而为MPD提供了重要的靶向治疗潜能。由于PDGFR、JAK2及C-KIT在骨髓造血中发挥着重要作用,提示伊马替尼可能正是通过阻滞PDGFR、JAK2V617F及C-KIT受体磷酸化阻断受体的信号传导通路,打断细胞分化增殖反应,从而起到治疗效果。本文总结伊马替尼在血小板增多症及其他骨髓增殖性疾病中的研究和应用,并探究其中的可能机制。
Imatinib mesylate has been commonly used in the treatment of patients with chronic myeloid leukemia （CML）. However, a significant number of CML patients treated with imatinib developed thrombocytopenia, oligocythemia, granulocytopenia. It has been confirmed that imatinib not only inhibits BCR-ABL mutations, but also suppresses other tyrosine kinase receptor genes such as PDGFR, JAK2V617F and C-KIT mutations, providing an important potential of targeted therapy for myeloproliferative disease. As the PDGFR, JAK2 and C-KIT play important roles in the regulation of hematopoiesis, suggesting that imatinib may block the phosphorylation of PDGFR, JAK2V617F and C-KIT receptors, interrupt the signal transduction cascades, disrupt cell differentiation and proliferation. In this review, the application and the potential molecular mechanism of imatinib in the treatment of thrombocythemia and other myeloproliferative diseases are discussed.
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2012年第6期1507-1512,共6页
Journal of Experimental Hematology
