The Philadelphia chromosome translocation t(9;22) creates a BCR-ABL fusion protein. The resulting constitutively active enzyme is BEST described as a:

• A Constitutively active serine-threonine kinase that phosphorylates RB1
• B Gain-of-function transcription factor that upregulates MYC
• C GTPase-deficient RAS protein locked in GTP-bound active state
• D Constitutively active tyrosine kinase that bypasses normal receptor-ligand activation ✓

Explanation

The BCR-ABL fusion protein (p210 or p185) possesses constitutively active tyrosine kinase activity because the BCR fusion partner disrupts the autoinhibitory structure of ABL1, keeping the kinase continuously active independent of extracellular signals. It phosphorylates multiple downstream substrates activating RAS, PI3K/AKT, and STAT5 pathways, driving CML/ALL. Imatinib and subsequent TKIs competitively inhibit the ATP-binding domain of BCR-ABL.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.