A 55-year-old man has leukocytosis of 120 × 10⁹/L with the full myeloid spectrum (blasts 3%, myelocytes, metamyelocytes, bands, neutrophils), basophilia, eosinophilia, and splenomegaly. BCR-ABL1 fusion gene is confirmed. The mechanism by which the BCR-ABL1 oncoprotein causes CML is:

• A Nuclear transcription factor activating differentiation and apoptosis programs
• B Constitutively active tyrosine kinase activating RAS-MAPK, JAK-STAT, and PI3K-AKT pathways, blocking apoptosis and promoting proliferation ✓
• C G protein-coupled receptor constitutively activating adenylyl cyclase
• D Serine-threonine kinase promoting MEK-ERK signaling exclusively

Explanation

The t(9;22)(q34;q11) Philadelphia chromosome creates the BCR-ABL1 fusion gene encoding a constitutively active tyrosine kinase. This kinase phosphorylates multiple substrates, activating proliferative pathways (RAS-MAPK, PI3K-AKT/mTOR, JAK-STAT5) and anti-apoptotic survival signals (BCL-XL, MCL-1 upregulation) in myeloid progenitors — causing the dramatic expansion of the myeloid clone seen in CML. Imatinib and subsequent TKIs competitively block the ABL kinase ATP-binding domain, achieving durable molecular remissions.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.