5-Aminoimidazole-4-carboxamide ribonucleoside induces differentiation of acute myeloid leukemia cells
5-Aminoimidazole-4-carboxamide ribonucleoside induces differentiation of acute myeloid leukemia cells
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DOI：
10.3109/10428194.2013.876633
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发表时间：
2014-10-01
影响因子：
2.6
通讯作者：
Visnjic, Dora
中科院分区：
文献类型：
--
作者：
Lalic, Hrvoje;Dembitz, Vilma;Visnjic, Dora
单磷酸腺苷 (AMP) 激活激酶 (AMPK) 调节剂已被证明在血液恶性肿瘤中发挥细胞毒活性，但其在急性髓系白血病 (AML) 分化中的作用尚不清楚。在这项研究中，研究了 AMPK 激动剂对全反式视黄酸 (ATRA) 介导的急性早幼粒细胞白血病 (APL) 和非 APL AML 细胞系分化的影响。结果表明，AMPK激动剂抑制成髓细胞HL-60、早幼粒细胞NB4和单核细胞U937的生长。 5-氨基咪唑-4-甲酰胺核糖核苷 (AICAR) 是一种 AMPK 激活剂，可增强 ATRA 介导的 NB4 细胞分化。在 U937 细胞中，AICAR 单独诱导与成熟单核细胞和巨噬细胞相关的细胞表面标志物的表达。在这两种细胞系中，AICAR 都会增加丝裂原激活蛋白激酶 (MAPK) 的活性，而 MAPK 抑制剂的存在会降低分化标记物的表达。这些结果揭示了 AICAR 对 AML 的有益作用，包括非 APL AML 细胞的分化。
Adenosine monophosphate (AMP)-activated kinase (AMPK) modulators have been shown to exert cytotoxic activity in hematological malignancies, but their role in the differentiation of acute myeloid leukemia (AML) is less explored. In this study, the effects of AMPK agonists on all-trans retinoic acid (ATRA)-mediated differentiation of acute promyelocytic leukemia (APL) and non-APL AML cell lines were investigated. The results show that AMPK agonists inhibit the growth of myeloblastic HL-60, promyelocytic NB4 and monocytic U937 cells. 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR), an AMPK activator, enhances ATRA-mediated differentiation of NB4 cells. In U937 cells, AICAR alone induces the expression of cell surface markers associated with mature monocytes and macrophages. In both cell lines, AICAR increases the activity of mitogen-activated protein kinase (MAPK), and the presence of a MAPK inhibitor reduces the expression of differentiation markers. These results reveal beneficial effects of AICAR in AML, including differentiation of non-APL AML cells.