In chronic myeloid leukemia (CML), the BCR-ABL1 fusion protein of the p210 isoform constitutively activates which downstream signaling pathway primarily responsible for anti-apoptotic survival?

• A NOTCH pathway
• B Hedgehog-GLI pathway
• C PI3K-AKT-mTOR pathway ✓
• D TGF-beta-SMAD pathway

Explanation

The BCR-ABL1 kinase in CML constitutively activates multiple downstream signaling cascades, but PI3K-AKT-mTOR is the primary pathway mediating anti-apoptotic survival signals by phosphorylating and inactivating pro-apoptotic factors such as BAD. RAS-MAPK (proliferation) and JAK-STAT (survival and differentiation) are also activated. The NOTCH, Hedgehog, and TGF-beta pathways are not direct downstream targets of BCR-ABL1.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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