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

Journal of biosciences

Jian Gu¹  Sai-Juan Chen¹  Zhu Chen1¹  Ji-Wang Zhang¹  Zhen-Yi Wang¹ 

[1] Shanghai Institute of Hematology, Ruijin Hospital Affiliated to Shanghai Second Medical University, 197 Ruijin Road II, Shanghai 200025, People’s Republic of China$$

关键词: Acute promyelocytic leukemia;    differentiation;    retinoic acid;   

DOI  :  

来源: Indian Academy of Sciences

【 摘 要 】

Retinoic acids (RA) play a key role in myeloid differentiation through their agonistic nuclear receptors (RAR𝛼/RXR) to modulate the expression of target genes. In acute promyelocytic leukemia (APL) cells with rearrangement of retinoic acid receptor 𝛼 (RAR𝛼) (including: PML-RAR𝛼, PLZF-RAR𝛼, NPM-RAR𝛼, NuMA-RAR𝛼 or STAT5b-RAR𝛼) 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-RAR𝛼 and its interaction with the nuclear receptor co-repressor complex, which restores the wild-type RAR𝛼/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.

【 授权许可】

Unknown