慢性髓系白血病粘附相关分子整合素β1及局部粘附激酶的研究

Study of adhesion-related moleculeβ1-integrin and focal adhesion kinase in chronic myeloid leukemia

目的研究整合素β1及局部粘附激酶(FAK)在慢性髓系白血病(CML)进展过程中的变化及干扰素治疗对FAK的可能作用。方法(1)应用流式细胞仪检测正常对照组、CML慢性期组及CML急变组骨髓CD34+细胞的胞膜表面CD29及胞质FAK表达量;(2)将正常对照及CML慢性期骨髓单个核细胞分为IFN处理组及非处理组培养48 h后提取总蛋白,应用Western blotting检测FAK含量变化。结果(1)CML慢性期骨髓CD34+细胞表面CD29的表达与对照组无显著差异,而胞内FAK含量则下降;(2)CML急变期骨髓CD34+细胞表面CD29的表达较慢性期明显升高而胞内FAK含量则较慢性期进一步下降;(3)IFN处理前后正常骨髓单个核细胞FAK的含量无明显差异;(4)IFN处理后CML骨髓单个核细胞FAK含量较未处理组明显上升。结论整合素β1及FAK表达变化可能是CML进展恶化的原因之一,而IFN-α可能通过恢复FAK含量来改善β1受体介导的粘附信号通路的缺陷。

Objective To study the changes in the expressions of β1-integrin receptor (CD29) and focal adhesion kinase (FAK) during the deterioration of chronic myeloid leukemia (CML), thereby explore the potential mechanism of interferon (IFN)-αin the treatment of CML through testing the quantitative changes of FAK. Methods Bone marrow mononuclear cells were tested for CD34, CD29 and FAK monoclonal antibody by flow cytometry in CML patients of the chronic phase and blast crisis and in normal subjects. In the presence or absence of IFN-α, the bone marrow mononuclear cells from CML patients of chronic phase and normal subjects were cultured for 48 h to determine the content of FAK in the cells with Western blotting. Results CD 29 expression on the surface of CD34 + cells scarcely differ between normal subjects and CML patients of chronic-phase, but the intracellular content of FAK was lower in the latter. The expression of β1-integrin receptor on the surface of hematopoietic cells in CML patients with blast crisis was significantly higher than that in chronic-phase CML patients, but the intracellular FAK in the former patients was lower. No difference of FAK content was observed in normal mononuclear cells before and after IFN-αtreatment, while the treatment increased FAK content in the mononuclear cells in chronic phase CML patients. Conclusion The changes in the expressions of β1-integrin receptor and FAK may play important roles during CML deteriora- tion, and IFN-αmay function to repair the defect in the β1-integrin receptor pathway by restoring the cellular content of FAK.