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mda-7/IL-24and IL-24 delE5 induce myeloid leukemia cells to differentiate into monocytes
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Abstract:
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-24and 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-24and its splice variant IL-24 delE5 expressions.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No. 30872983, 81070426), and the Key Program of Applied Basic Research Foundation of Tianjin (No. 11JCZDJC18000)
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