All-trans retinoic acid induces complete remission in acute promyelocytic leukemia primarily by which mechanism?
- A Inhibiting the tyrosine kinase activity of PML-RARA
- B Displacing corepressors from the RAR-alpha moiety of PML-RARA, allowing transcription of genes that drive granulocytic differentiation ✓
- C Promoting apoptosis of promyelocytes by blocking BCL-2
- D Downregulating MYC expression through degradation of the PML portion of the fusion protein
Correct answer: B. Displacing corepressors from the RAR-alpha moiety of PML-RARA, allowing transcription of genes that drive granulocytic differentiation
Explanation
PML-RARA represses myeloid differentiation genes by recruiting corepressors and histone deacetylases to the retinoic acid receptor domain. Pharmacologic doses of all-trans retinoic acid bind this domain, release the corepressor complex, and restore transcription, causing the malignant promyelocytes to mature into neutrophils. It does not inhibit kinase activity, and its dominant effect is differentiation, not direct apoptosis.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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