The PML-RARα fusion oncoprotein in APL drives leukemogenesis primarily by:
- A Constitutively activating JAK2 kinase signaling
- B Blocking myeloid differentiation by aberrant transcriptional repression at retinoic acid response elements ✓
- C Inhibiting BCL-2-mediated apoptosis through BH3 domain sequestration
- D Upregulating c-KIT ligand autocrine loops
Correct answer: B. Blocking myeloid differentiation by aberrant transcriptional repression at retinoic acid response elements
Explanation
In APL, the t(15;17) translocation fuses PML to RARα. The fusion protein binds retinoic acid response elements with much higher affinity and recruits co-repressor complexes (HDAC, NCoR), blocking transcription of genes required for myeloid differentiation. Pharmacologic doses of ATRA displace co-repressors, restore transcription, and force terminal differentiation. JAK2 activation is the mechanism in polycythemia vera; BCL-2 sequestration underlies venetoclax sensitivity in CLL/AML without the fusion.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.