The BCR-ABL1 fusion in chronic myeloid leukemia results from t(9;22). The constitutively active tyrosine kinase produced preferentially phosphorylates substrates that activate which downstream pathway responsible for leukemic proliferation?

• A JAK-STAT pathway only
• B WNT-beta-catenin pathway exclusively
• C NF-kB pathway through direct IkB phosphorylation
• D RAS-MAPK and PI3K-AKT pathways, promoting proliferation and inhibiting apoptosis ✓

Explanation

BCR-ABL1 is a constitutively active tyrosine kinase that signals through multiple pathways including RAS-MAPK (promoting proliferation) and PI3K-AKT (inhibiting apoptosis). It also activates JAK-STAT and NF-kB but the dominant oncogenic signaling is RAS/MAPK and PI3K/AKT. Imatinib targets the ATP-binding site of ABL1 to block all these downstream effects.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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