In chronic myeloid leukemia (CML), the BCR-ABL1 p210 fusion protein drives leukemogenesis primarily by constitutive activation of which downstream pathway that confers growth factor independence?

• A JAK2-STAT5 signaling exclusively via cytokine receptor mimicry
• B RAS-RAF-MAPK and PI3K-AKT-mTOR pathways via constitutive tyrosine kinase activity ✓
• C NF-kB pathway via BCR-ABL1-mediated IKK activation solely
• D CDK4/6-Rb pathway via BCR-ABL1-induced cyclin D1 transcription

Explanation

BCR-ABL1 p210 is a constitutively active tyrosine kinase that signals through multiple downstream pathways simultaneously, including RAS-RAF-MEK-ERK (proliferation), PI3K-AKT-mTOR (survival and growth), and STAT5 (anti-apoptosis). This multivalent signaling confers growth factor independence and blocks apoptosis. While STAT5 and NF-kB are activated, the critical driver of proliferative independence is the combined RAS-MAPK and PI3K-AKT activation. CDK4/6-Rb is a downstream consequence of multiple oncogenic signals but is not the primary BCR-ABL1 effector.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.