A patient with AML shows t(15;17) on karyotyping. The PML-RARα fusion protein in APL causes disease primarily by:
- A Constitutive activation of tyrosine kinase signaling
- B Blocking myeloid differentiation at the promyelocyte stage by dominant-negative RAR repression ✓
- C Hypermethylation of BCL2 promoter inducing apoptosis
- D Deletion of chromosome 5q causing haploinsufficiency of RPS14
Correct answer: B. Blocking myeloid differentiation at the promyelocyte stage by dominant-negative RAR repression
Explanation
The PML-RARα fusion protein acts as a dominant-negative repressor of retinoic acid receptor signaling, blocking myeloid differentiation and locking cells at the promyelocyte stage. Pharmacologic doses of all-trans retinoic acid (ATRA) overcome this block, inducing differentiation — this is the basis of ATRA therapy in APL. Tyrosine kinase activation is the mechanism in BCR-ABL CML.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.