Imatinib mesylate (STI571) decreases the vascular endothelial growth factor plasma concentration in patients with chronic myeloid leukemia
Imatinib mesylate (STI571) decreases the vascular endothelial growth factor plasma concentration in patients with chronic myeloid leukemia
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DOI：
10.1182/blood-2003-08-2695
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发表时间：
2004-07-15
期刊：
影响因子：
20.3
通讯作者：
Pagès, G
中科院分区：
文献类型：
--
作者：
Legros, L;Bourcier, C;Pagès, G
慢性髓系白血病(CML)是一种表达嵌合bcr/abl蛋白的克隆性骨髓增殖性疾病，骨髓血管生成增加是慢性髓系白血病的特征之一。最近，随着一种新药的开发，CML的治疗策略已经完全改变：甲磺酸伊马替尼(STI571)，一种BCR/Abl酪氨酸激酶活性的特异性抑制剂。我们研究的目的是，在慢性粒细胞白血病患者中，确定甲磺酸伊马替尼对血管生成最有效的调节因子之一血管内皮生长因子(VEGF)的调节能力。在新诊断的CML中，我们观察到CML BM细胞分泌的血管内皮生长因子显著增加，血浆中的血管内皮生长因子浓度显著升高。我们认为低浓度的血浆血管内皮生长因子可能是细胞遗传学完全缓解的特征之一。为了了解伊马替尼抑制血管内皮生长因子产生的分子机制，我们将实验集中在bcr/abl阳性的人细胞系K562上。我们证明伊马替尼通过靶向Sp1和Sp3转录因子来抑制血管内皮细胞生长因子的转录。综上所述，我们的结果强调了血管内皮生长因子浓度在评估接受伊马替尼治疗的CML患者的演变方面的潜在预后价值。(C)2004年，由美国血液病学会提供。
Increased angiogenesis in bone marrow (BM) is one of the characteristics of chronic myeloid leukemia (CML), a clonal myeloproliferative disorder that expresses a chimeric Bcr/Abl protein. Recently, the therapeutic strategy in CML has been totally modified with the development of a new drug: imatinib mesylate (STI571), a specific inhibitor of Bcr/Abl tyrosine kinase activity. The aim of our study was to determine, in patients with CML, the capacity of imatinib mesylate to modulate one of the most potent regulators of angiogenesis, the vascular endothelial growth factor (VEGF). In newly diagnosed CML, we observed significantly increased VEGF secretion by CML BM cells and significantly increased VEGF plasma concentrations. We showed that low plasma VEGF concentrations could be one of the characteristics of complete cytogenetic remission. To understand the molecular mechanisms leading to the inhibition of VEGF production by imatinib, we focused our experiments on the human cell line K562, which is Bcr/Abl positive. We demonstrated that imatinib inhibits VEGF gene transcription by targeting the Sp1 and Sp3 transcription factors. Taken together, our results highlight the potential prognostic value of VEGF concentrations in evaluating the evolution of CML patients treated with imatinib. (C) 2004 by The American Society of Hematology.