A 68-year-old man presents with fatigue, night sweats, and splenomegaly. CBC shows WBC 85,000/µL with a left shift (blasts 2%, promyelocytes 5%, myelocytes 12%, bands 18%, segmented neutrophils 55%, basophilia, eosinophilia). Bone marrow biopsy is hypercellular with predominant granulocytic proliferation. Cytogenetics reveals t(9;22)(q34;q11). Which fusion protein drives this disease?

• A PML-RARα — a constitutively active transcription repressor
• B BCR-ABL1 — a constitutively active tyrosine kinase ✓
• C AML1-ETO — a dominant negative transcription factor
• D FLT3-ITD — an internal tandem duplication kinase

Explanation

The Philadelphia chromosome t(9;22) creates the BCR-ABL1 fusion oncogene, which encodes a constitutively active non-receptor tyrosine kinase that drives uncontrolled granulocyte proliferation. This is the defining molecular lesion of chronic myelogenous leukemia (CML). PML-RARα is associated with acute promyelocytic leukemia (AML M3); AML1-ETO with AML M2; FLT3-ITD with AML, particularly the normal-karyotype subtype.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.