包含阿克拉霉素、阿糖胞苷和粒细胞集落刺激因子（G-CSF）的化疗方案在国内和日本被广泛应用于急性髓性白血病（AML）的治疗。CAG化疗方案的作用机制还不十分明确。骨髓基质细胞对白血病细胞的保护和白血病细胞的增殖行为影响临床治疗效果。我们以前的研究发现miR-146a通过调控Smad4蛋白的表达影响细胞的增殖。本课题以AML细胞株和病人原代白血病细胞为研究对象。从信号传导角度观察G-CSF作用前后，NF-κB→miRNA146a→CXCR4/Smad4途径中关键因子的变化；从细胞增殖、趋化角度，观察G-CSF作用后，CXCR4和Smad4表达下降,是否增加小剂量的阿克拉霉素和阿糖胞苷对白血病细胞的杀伤作用。在完善我们对miR-146a在CAG化疗方案中调控机制的理解基础上，明确能否根据患者血浆内的miR-146a的表达，作为判断治疗预后的临床标志物，为白血病的特异性分层治疗提供可能的方向。

The regimen of cytarabine, aclarubicin and G-CSF (CAG) has been widely used in China and Japan for treatment of acute myeloid leukemia (AML) . The rationale for the regimen is still not very clear. The clinical therapeutic effects may be affected by the protection of stromal cells on leukemia cells and leukemia cells proliferation biological behaviours. We found the expression of Smad4 protien was regulated by miR-146a expression level and had effects on cell proliferation. Acute myeloid leukemia cell lines and leukemia cells from patients will be research in this study. NF-κB→miRNA146a→CXCR4/Smad4 pathway will be investigated on with or without G-CSF treatment based signal transduction. The relationship of decreasing expression CXCR4/Smad4 and increasing the anti-leukemia cells effect of low dose clarubicin and cytarabine will be investigated with or without G-CSF treatment based on cell proliferation and chemotaxis. Based on leukemia cells homing mechanisms being regulated by miR-146a in CAG regimen, we want to confirm the expression levels of miR-146a in patient plasma as a prognosis biomarker which can be used in clinic. This will provide a trend in leukemia chemotherapy.