A 34-year-old woman presents with gum bleeding and ecchymoses. CBC shows Hb 8.5 g/dL, WBC 12,000/μL, platelets 18,000/μL. Bone marrow shows hypergranular promyelocytes with abundant Auer rods in bundles. FISH reveals t(15;17). What is the key molecular consequence of this translocation?
- A Block in myeloid differentiation due to PML-RARalpha fusion protein impairing retinoic acid signaling ✓
- B Constitutive activation of the ABL tyrosine kinase due to BCR-ABL fusion
- C Dysregulation of the MYC oncogene driving uncontrolled proliferation
- D Loss of the RARalpha gene leading to defective apoptosis
Correct answer: A. Block in myeloid differentiation due to PML-RARalpha fusion protein impairing retinoic acid signaling
Explanation
t(15;17) produces the PML-RARalpha fusion protein, which dominantly blocks retinoic acid receptor signaling and arrests myeloid maturation at the promyelocyte stage (APL). All-trans retinoic acid (ATRA) overcomes this block. BCR-ABL is t(9;22) in CML. MYC dysregulation is characteristic of Burkitt lymphoma (t(8;14)). RARalpha is not lost but fused.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.