In acute promyelocytic leukemia (APL), the fusion protein PML-RARα causes leukemogenesis primarily by:

• A Constitutively activating JAK2 kinase signalling
• B Amplifying MYC transcription
• C Inhibiting apoptosis via BCL2 upregulation
• D Blocking myeloid differentiation by recruiting co-repressors to retinoic acid target genes ✓

Explanation

The t(15;17) translocation produces PML-RARα, which recruits histone deacetylase (HDAC) and nuclear co-repressor complexes to retinoic acid response elements at physiological concentrations of retinoic acid, blocking the transcription of genes needed for granulocytic differentiation and trapping cells at the promyelocyte stage. All-trans retinoic acid (ATRA) at pharmacological doses overcomes this block by inducing conformational change and co-repressor release. JAK2 mutations are characteristic of myeloproliferative neoplasms, not APL.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.