Hypoxia inducible factor-1alpha and leukemic cell differentiation.
Arsenic trioxide (As2O3, 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.
Chen
Guo-Qiang
GQ
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. chengq@shsmu.edu.cn
Peng
Zhen-Gang
ZG
Liu
Wei
W
Song
Li-Ping
LP
Jiang
Yi
Y
Huang
Ying
Y
Zhao
Qian
Q
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000494:pharmacology*; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology*; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000473:pathology; D010087:Oxides / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001152:Arsenicals; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010087:Oxides; D000077237:Arsenic Trioxide