Cytogenetic analysis of bone marrow from a patient with pancytopenia and circulating abnormal promyelocytes reveals t(15;17)(q24;q21). The fusion protein produced blocks myeloid differentiation at the promyelocyte stage by sequestering retinoic acid receptor co-repressor complexes. Which therapeutic agent directly overcomes this differentiation block?
- A Imatinib
- B Rituximab
- C All-trans retinoic acid ✓
- D Hydroxyurea
Correct answer: C. All-trans retinoic acid
Explanation
t(15;17) generates the PML-RARA fusion of acute promyelocytic leukemia, a subtype of AML-M3. The fusion retains retinoic acid binding domains but recruits excessive corepressors, blocking granulocytic differentiation. Pharmacologic doses of all-trans retinoic acid force the fusion protein to release corepressors, restoring differentiation and triggering maturation of blasts, often with a transient differentiation syndrome. Imatinib targets BCR-ABL in CML, rituximab targets CD20 in C-cell lymphomas, and hydroxyurea has no role here.
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.