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为探讨ABL酪氨酸激酶特异性抑制剂STI5 71(CGP5 7148B)对Ph(+ )慢性髓性白血病(CML)的疗效机制 ,观察了STI5 71预处理 (0 .1μmol/L× 30 - 60min)前后 β1整合素活化剂及纤连蛋白 (FN)单独或联合作用以及STI5 71预处理本身对正常及CML粒巨噬系集落形成单位(CFU GM )的影响 ,并结合阻断实验观察了VLA 4及VLA 5整合素在其中的作用。结果显示 :①STI5 71预处理、β1整合素活化剂单独或联合作用或FN单独作用对CML及正常CFU GM均无明显抑制作用 ,STI5 71预处理对活化剂或FN的作用也无直接影响 ;② β1整合素活化剂 +FN对CMLCFU GM抑制作用明显低于对正常CFU GM的作用 ;③经STI5 71预处理后 ,活化剂 +FN对CMLCFU GM抑制作用明显提高达正常水平 ;④阻断VLA4 +VLA5整合素或总 β1整合素可阻断STI5 71的上述作用。研究结果提示STI5 71提高Ph(+ )CML祖细胞 β1整合素介导的增殖抑制作用
To investigate the mechanism of ABL tyrosine kinase specific inhibitor STI5 71 (CGP5 7148B) in Ph(+) chronic myelogenous leukemia (CML), STI5 71 pretreatment (0.1 μmol/L × 30 - 60 min) was observed. Effects of β1 integrin activator and fibronectin (FN) alone or in combination, and STI5 71 pretreatment itself on normal and CML macrophage colony forming units (CFU GM ), and combined with blocking experiments to observe VLA 4 And the role of VLA 5 integrin in it. The results showed that: 1 STI5 71 pretreatment, β1 integrin activator alone or in combination or FN alone had no significant inhibitory effect on CML and normal CFU GM, STI5 71 pretreatment had no direct effect on the role of activator or FN; 2 The inhibitory effect of β1 integrin activator + FN on CMLCFU GM was significantly lower than that of normal CFU GM; 3 After STI5 71 pretreatment, the inhibitory effect of activator + FN on CMLCFU GM was significantly increased to normal levels; 4 VLA4 + was blocked VLA5 integrin or total β1 integrin can block the above effects of STI5 71. The results suggest that STI5 71 enhances β1 integrin-mediated proliferation inhibition in Ph(+) CML progenitor cells