Over-expression of Mcl-l impairs the ability of ATRA to induce growth arrest and differentiation in acute promyelocytic leukemia cells.
Over-expression of Mcl-l impairs the ability of ATRA to induce growth arrest and differentiation in acute promyelocytic leukemia cells.
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Mcl-1 的过度表达会损害 ATRA 诱导急性早幼粒细胞白血病细胞生长停滞和分化的能力。
DOI：
10.1007/s10495-013-0872-0
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发表时间：
2013
期刊：
影响因子：
7.2
通讯作者：
Yokovama A.
中科院分区：
文献类型：
--
作者：
Yang J;lkezoe T;Nishioka C;Yokovama A.
急性早幼粒细胞白血病（APL）细胞暴露于全反式维甲酸（ATRA）可增加Mcl-1的水平，然而，ATRA介导的Mcl-1在这些细胞中的表达的意义仍有待充分阐明。本研究发现，NB 4和PL-21细胞暴露于ATRA增加与c-jun N-末端激酶磷酸化相关的Mcl-1水平。小干扰（siRNA）或JNK抑制剂下调Mcl-1显着增强ATRA诱导这些细胞分化和凋亡的能力。另一方面，当Mcl-1在NB 4和PL-21细胞以及从APL个体分离的白血病细胞中强制表达时，ATRA的抗白血病作用减弱。此外，通过siRNA下调Mcl-1使非APL U937和KG-1白血病细胞对ATRA介导的分化和凋亡敏感。总之，抑制Mcl-1可能有助于增强ATRA在APL和非APL AML细胞中的作用。
Exposure of acute promyelocytic leukemia (APL) cells to all-trans retinoic acid (ATRA) increases levels of Mcl-1, however, the implication of ATRA-mediated expressions of Mcl-1 in these cells remains to be fully elucidated. This study found that exposure of NB4 and PL-21 cells to ATRA increased levels of Mcl-1 in association with phosphorylation of c-jun N-terminus kinases. Down-regulation of Mcl-1 by a small interfering (siRNA) or an inhibitor of JNK significantly potentiated the ability of ATRA to induce differentiation and apoptosis in these cells. On the other hand, the anti-leukemia effects of ATRA were blunted when Mcl-1 was forced expressed in NB4 and PL-21 cells as well as leukemia cells isolated from individuals with APL. Furthermore, down-regulation of Mcl-1 by an siRNA sensitized non-APL U937 and KG-1 leukemia cells to ATRA-mediated differentiation and apoptosis. Taken together, inhibition of Mcl-1 might be useful to potentiate the action of ATRA in APL as well as non-APL AML cells.