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 ofall-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.
Volume 46, 2020
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