目的：研究人黑素瘤分化相关基因-7（melanoma differentiation associated gene-7，mda-7；又称IL-24）及其剪接体IL-24 delE5与急性髓系白血病（acute myeloid leukemia，AML）细胞分化的关系。方法：十四烷酰佛波醇-乙酯（12-O-tetradecanoylphorbol-13-acetate，TPA）处理人急性髓系白血病细胞系U937、HL-60，real-time PCR及Western blotting检测细胞中mda-7/IL-24和IL-24 delE5的表达，FACS检测细胞表面CD11b、CD14和CD115的表达。siRNA干扰U937、HL-60细胞中mda-7/IL-24和IL-24 delE5的表达后，再以TPA诱导细胞分化，FACS检测CD11b、CD14和CD115的表达。用前期构建的mda-7/IL-24和IL-24 delE5载体转染U937、HL-60及AML-M5患者的原代白血病细胞，观察异位过表达mda-7/IL-24和IL-24 delE5能否诱导白血病细胞向单核细胞分化。结果：TPA在诱导U937、HL-60细胞向单核细胞分化过程中显著促进mda-7/IL-24及其剪接体IL-24 delE5的表达，用siRNA干扰mda-7/IL-24及IL-24 delE5的表达后，TPA诱导U937、HL-60细胞向单核细胞分化的作用也被阻断。异位过表达mda-7/IL-24和IL-24 delE5可诱导U937、HL-60以及原代AML细胞向单核细胞分化：U937、HL-60细胞表面CD11b和CD14表达均显著升高，CD115表达仅在U937细胞有显著升高；3例AML-M5患者的原代AML细胞中CD11b、CD14及CD115表达均有不同程度升高，细胞呈现单核细胞的形态特征。结论：TPA可通过上调mda-7/IL-24及其剪接体IL-24 delE5的表达诱导白血病细胞向单核细胞分化。

Objective:To investigate the effects of melanoma differentiation associated gene-7 (mda-7, also named IL-24) and IL-24 delE5, an mda-7/IL-24 splice variant, on differentiation of acute myeloid leukemia (AML) cells. Methods: The AML cell lines U937 and HL-60 were treated with 12-O-tetradecanoylphorbol-13-acetate (TPA); mda-7/IL-24 and IL-24 delE5 expressions were detected by real-time PCR and Western blotting assays. CD11b, CD14 and CD115 expressions on cell surface were examined by FACS. U937 and HL-60 cells were induced with TPA after siRNA interfering mda-7/IL-24 and IL-24 delE5 expressions, and then CD11b, CD14 and CD115 expressions were examined by FACS. U937 and HL-60 cell lines and primary leukemia cells from AML-M5 patients were transfected with mda-7/IL-24 or IL-24 delE5 plasmids, which were established in our previous study, in order to know whether ectopic overexpressions of mda-7/IL-24and IL-24 delE5 can induce the monocytic differentiation of leukemia cells. Results: The expressions of mda-7/IL-24 and its splice variant, IL-24 delE5, were significantly induced in U937 and HL-60 cells during TPA-mediated monocytic differentiation. Interfering mda-7/IL-24 and IL-24 delE5 expressions after siRNA treatment inhibited the monocytic differentiation ability of TPA on U937 and HL-60 cells. Ectopic overexpressions of mda-7/IL-24 and IL-24 delE5 induced differentiation of U937, HL-60, and primary AML leukemia cells into monocytes: CD11b, CD14 expressions on U937 and HL-60 cells and CD115 expression on U937 were significantly increased; CD11b, CD14 and CD115 expressions on primary leukemia cells from 3 AML patients were also increased with monocytic features. Conclusion: TPA can induce monocytic differentiation of leukemia cells by increasing mda-7/IL-24and its splice variant IL-24 delE5 expressions.

国家自然科学基金资助项目（No. 30872983，81070426）；天津市应用基础研究基金重点资助项目（No. 11JCZDJC18000）