Serum KIT and KIT ligand levels in patients with gastrointestinal stromal tumors treated with imatinib
Serum KIT and KIT ligand levels in patients with gastrointestinal stromal tumors treated with imatinib
复制标题
DOI：
10.1182/blood-2003-10-3443
复制
发表时间：
2004-04-15
期刊：
影响因子：
20.3
通讯作者：
Joensuu, H
中科院分区：
文献类型：
--
作者：
Bono, P;Krause, A;Joensuu, H
甲磺酸伊马替尼是包括KIT在内的几种酪氨酸激酶的选择性抑制剂，是治疗胃肠道间质瘤（gist）的首选有效药物。在一项前瞻性随机试验中，我们监测了接受伊马替尼治疗的晚期gist患者血清中KIT、KIT配体（干细胞因子，SCIF）和血管内皮生长因子（VEGF）的水平。与对照组相比，gist患者（n = 66）的预处理血清KIT和VEGF水平升高（中位数为292 AU/mL [409 ng/mL] vs 238 AU/mL [333 ng/mL]， P = 0.037；中位数为303 pg/mL vs 190 pg/mL， P = 0.013），但SCIF水平较低（中位数为645 pg/mL vs 950 pg/mL， P小于或等于0.0001）。伊马替尼治疗1个月和6个月后，平均血清KIT水平较预处理水平分别下降31%和52%，而SCIF水平分别上升11%和33%。有反应的患者在治疗期间血清VEGF水平下降。血清SCF/KIT比值中位数随着治疗时间的延长而增加，治疗12个月后比基线时高出7.7倍（范围为3.1-259倍）。高血清SCF/KIT比值可能会增加SCF诱导的细胞信号转导与伊马替尼治疗的延长，当伊马替尼治疗停止时，以及GIST有野生型受体的患者。(C) 2004年由美国血液病学会出版。
Imatinib mesylate is a selective inhibitor of a few tyrosine kinases including KIT, and it is the first effective treatment for gastrointestinal stromal tumors (GISTs). We monitored the serum levels of KIT, KIT ligand (stem cell factor, SCIF), and the vascular endothelial growth factor (VEGF) in patients with advanced GISTs treated with imatinib in a prospective randomized trial. Patients with GISTs (n = 66) had elevated pretreatment serum KIT and VEGF levels as compared with controls (median, 292 AU/mL [409 ng/mL] vs 238 AU/mL [333 ng/mL], P = .037; and median, 303 pg/mL vs 190 pg/mL, P = .013, respectively), but lower levels of SCIF (median, 645 pg/mL vs 950 pg/mL; P less than or equal to .0001). After 1 and 6 months of imatinib treatment the average serum KIT levels decreased 31% and 52% from pretreatment levels, whereas SCIF levels increased 11% and 33%, respectively. Serum VEGF levels decreased during treatment in responding patients. The median serum SCF/KIT ratio increased with treatment duration, and was 7.7-fold higher after 12 months of treatment than at baseline (range, 3.1-259-fold). A high serum SCF/KIT ratio may increase SCF-induced cell signaling with prolonged imatinib treatment, at the time when imatinib treatment is withdrawn, and in patients whose GIST has wild-type receptors. (C) 2004 by The American Society of Hematology.