title: Mechanisms of all-trans retinoic acid-induced differentiation of acute promyelocytic leukemia cells.
abstract: 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 a (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.
authors.affiliation: Shanghai Institute of Hematology, Ruijin Hospital Affiliated to Shanghai Second Medical University, 197 Ruijin Road II, Shanghai 200 025, People's Republic of China.
authors.forename: J W
authors.initials: JW
authors.lastname: Zhang
authors.forename: J Y
authors.initials: JY
authors.lastname: Wang
authors.forename: S J
authors.initials: SJ
authors.lastname: Chen
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000187:drug effects*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D018922:HL-60 Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D009363:Neoplasm Proteins / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins / Q000502:physiology; D056971:Nuclear Receptor Co-Repressor 1; D015514:Oncogene Proteins, Fusion / Q000187:drug effects* / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000819:agonists* / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D014178:Translocation, Genetic; D014212:Tretinoin / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C539127:NCOR1 protein, human; C120276:NPM-RARalpha protein, human; D009363:Neoplasm Proteins; C412764:NuMa-RARalpha protein, human; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D015514:Oncogene Proteins, Fusion; C118318:PLZF-RARalpha fusion protein, human; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D014157:Transcription Factors; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin