髓样细胞白血病-1基因在多发性骨髓瘤发病中的分子机制

Molecular mechanism of myeloid cell leukemia-1 for multiple myeloma

目的通过检测骨髓瘤细胞中依赖IL-6与否的髓样细胞白血病-1(mcl-1)基因的表达,阐明mcl-1基因在多发性骨髓瘤发病中的信号转导通路。方法应用JAK特异性抑制剂AG490、蛋白激酶抑制剂LY294002、ERK1/2信号通路的特异性阻断剂PD98059,分别研究了JAK/STAT通路、ras/MAPK通路及PI3K/Akt三大信号途径与mcl-1基因在多发性骨髓瘤中的关系。结果在骨髓瘤细胞8226和U266中,抑制ERK1/2活性不能改变mcl-1的表达;高浓度的AG490不能抑制STAT3的酪氨酸磷酸化;LY294002可抑制8226细胞和ANBL-6细胞的增殖,但不抑制mcl-1的表达。结论 Ras/MAPK通路以及PI3K通路在mcl-1基因的调节中无作用,但STAT的作用仍然需要进一步探讨。

Objective To clarify the signal transduction pathway of myeloid cell leukemia-1（mcl-1） gene in the pathogenesis of multiple myeloma via studying the mcl-1 gene expression of dependent and independent IL-6 in myeloma cells.Methods The JAK inhibitor AG490,protein kinase inhibitor LY294002,and ERK1/2 signaling pathway specific inhibitor PD98059 were used to explore the relationship between mcl-1 gene and the three signal pathways： JAK/STAT,Ras/MAPK and PI3K/Akt in multiple myeloma.Results In multiple myeloma cells（8226 and U266）,inhibition of ERK1/2 activity failed to change the expression of mcl-1.AG490,even at a high concentration,did not inhibit the tyrosine phosphorylation of STAT3;LY294002 inhibited the proliferation of 8226 and ANBL-6 cells,but it showed no inhibition on the expression of mcl-1.Conclusion Ras/MAPK pathway and PI3K pathway have no effect on the regulation of mcl-1 gene,but the role of STAT still needs further exploration.