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低氧诱导因子和白血病细胞分化

陈国强, 彭镇刚, 刘玮, 宋利平, 蒋益, 黄莺, 赵倩

上海交通大学医学院病理生理学教研室，细胞分化与凋亡教育部重点实验室. 上海 200025；中国科学院上海生命科学研究院健康科学研究所. 上海 200025

摘要

三氧化二砷(As_(2)O_(3), ATO)是一种新发现的有效治疗急性早幼粒细胞白血病(acute promyelocytic leukemia, APL)的药物。研究发现，该药物在体外诱导细胞分化的能力不如体内明显。以此为基础，最近我们意外地发现模拟低氧化合物和中度低氧环境能够直接在体外诱导急性髓系白血病细胞分化，也选择性地加强三氧化二砷诱导的APL细胞分化。进一步地，间歇性低氧能够显著延长移植的白血病小鼠生存时间，并且抑制白血病细胞浸润并诱导其分化。以这些工作为基础，作者就低氧诱导白血病细胞分化的分子机制进行了深入研究。 该文将就相关工作作一综述， 并讨论有待进一步研究的问题。

关键词： 白血病; 低氧诱导因子-1; CCAAT/增强子结合蛋白; 三氧化二砷; 细胞分化

Hypoxia inducible factor--1#alpha# and leukemic cell differentiation

Chen Guoqiang, Peng Zhengang, Liu Wei, Song Liping, Jiang Yi, Huang Ying, Zhao Qian

The Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education of China, School of Medical Sciences, Shanghai Jiaotong University. Shanghai 200025, China；Institute of Health Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. Shanghai 200025, China

Abstract

Arsenic trioxide (As_(2)O_(3), ATO) is a recently developed drug for the effective treatment of acute promyelocytic leukemia (APL). Experimental studies showed that in vitro differentiation-inducing ability on APL cells of this drug is not significant compared with its in vivo activity. We unexpectedly found recently that hypoxia-mimetic agents and moderate real hypoxia triggered acute myeloid leukemic cells to undergo differentiation. Furthermore, intermittent hypoxia significantly prolonged the survival of the transplanted leukemic mice with inhibition of infiltration and induction of differentiation of leukemic cells. In the following works, molecular mechanisms of hypoxia-induced differentiation were investigated and some interesting results have been obtained. This review will shortly summarize the related progresses and discuss the questions remained to be further investigated.

Key words: Leukemia;Hypoxia inducible factor-1;CCAAT/enhancer-binding protein-α;Arsenic trioxide;Differentiation

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引用本文：

陈国强, 彭镇刚, 刘玮, 宋利平, 蒋益, 黄莺, 赵倩. 低氧诱导因子和白血病细胞分化[J]. 生理学报 2006; 58 (1): .

Chen Guoqiang, Peng Zhengang, Liu Wei, Song Liping, Jiang Yi, Huang Ying, Zhao Qian. Hypoxia inducible factor--1#alpha# and leukemic cell differentiation. Acta Physiol Sin 2006; 58 (1): (in Chinese with English abstract).