低浓度STI571提高β1整合素介导的Ph(+)慢性髓性白血病髓系祖细胞增殖抑制  

Low Concentrations of STI571 Enhances β1 Integrin Mediated Inhibitory Effect on Proliferation of Myeloid Progenitors in Ph(+)Chronic Myeloid Leukemia

作　　者：白任奎[1] 陈珊珊[1] 刘艳荣[1] 李金兰[1] 付家瑜[1] 

机构地区：[1]北京大学人民医院,血液病研究所,北京100044

出　　处：《中国实验血液学杂志》2001年第3期207-211,共5页Journal of Experimental Hematology

基　　金：国家自然科学基金 ( 3 9870 846);国家教委博士点基金 ( 982 6)资助~~

摘　　要：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To investigate whether ABL specific tyrosine kinase specific inhibitor STI571 can restore β1 integrin mediated negative effect on Ph(+) chronic myeloid leukemia(CML), the inhibitory effect of beta 1 integrin activator(β1 integrin activating antibody 8A2, cytokines such as GM-CSF, G-CSF and SCF) and/or FN on the granulocyte-macrophage colony forming unit (CFU-GM) from 16 patients with Ph(+)CML and 13 normal individuals were examined; the bone marrow mononuclear cells (BMMNC) before and after ABL kinase specific inhibitor STI571 pretreatment(0.1 μmol/L for 30-60 minutes) were target cells in this study. The roles which VLA4 and VLA5 played in this process were evaluated through blocking assay. The results showed: ① β1 integrin activator(s) or FN alone have no effect on CFU-GM from CML or normal bone marrow mononuclear cells before or after STI571 pretreatment, nor STI571 pretreatment itself. ② The inhibitory effect of β1 integrin activator(s) plus FN on CML CFU-GM are significantly lower than that on normal CFU-GM. ③ The inhibitory effect of β1 integrin activator(s) plus FN on CML CFU-GM after STI571 pretreatment is comparable to that on normal CFU-GM. ④ Monoclonal antibody to VLA4 and VLA5 or to total β1 integrins almost completely abrogate the above effect of STI571. The results suggested enhancing β1 integrin mediated negative effect on myeloid progenitors in Ph(+)CML is one of the therapeutic mechanisms of STI571 on Ph(+)CML.

关 键 词：Ph(+)慢性髓性白血病 CML 整合素 CFU-GM 粒巨噬系集落形成单位 酪氨酸激酶抑制剂 

分 类 号：R733.72[医药卫生—肿瘤]