Mechanisms of all-trans retinoic acid-induced differentiation of acute promyelocytic leukemia cells

被引:74
作者
Zhang, JW [1 ]
Gu, J [1 ]
Wang, ZY [1 ]
Chen, SJ [1 ]
Chen, Z [1 ]
机构
[1] Shanghai Med Univ 2, Ruijin Hosp, Shanghai Inst Hematol, Shanghai 200025, Peoples R China
关键词
acute promyelocytic leukemia; differentiation; retinoic acid;
D O I
10.1007/BF02703936
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Retinoic acids (RA) play a key role in myeloid differentiation through their agonistic nuclear receptors (RAR alpha/RXR) to modulate the expression of target genes. In acute promyelocytic leukemia (APL) cells with rearrangement of retinoic acid receptor alpha (RAR alpha) (including: PML-RAR alpha, PLZF-RAR alpha, NPM-RAR alpha, NuMA-RAR alpha or STAT5b-RAR alpha) as a result of chromosomal translocations, the RA signal pathway is disrupted and myeloid differentiation is arrested at the promyelocytic stage. Pharmacologic dosage of all-trans retinoic acid (ATRA) directly modulates PML-RAR alpha and its interaction with the nuclear receptor co-repressor complex, which restores the wild-type RAR alpha/RXR regulatory pathway and induces the transcriptional expression of downstream genes. Analysing gene expression profiles in APL cells before and after ATRA treatment represents a useful approach to identify genes whose functions are involved in this new cancer treatment. A chronologically well coordinated modulation of ATRA-regulated genes has thus been revealed which seems to constitute a balanced functional network underlying decreased cellular proliferation, initiation and progression of maturation, and maintenance of cell survival before terminal differentiation.
引用
收藏
页码:275 / 284
页数:10
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