In T-cell acute lymphoblastic leukemia/lymphoma (T-ALL), the most commonly mutated signalling pathway drives transcription of target genes via intracellular domain cleavage. This pathway involves which protein?
- A FLT3
- B BCL2
- C NOTCH1 ✓
- D PTEN
Correct answer: C. NOTCH1
Explanation
NOTCH1 gain-of-function mutations are present in over 50% of T-ALL cases. Normally, gamma-secretase cleaves NOTCH1 after ligand binding, releasing the intracellular domain (NICD) which translocates to the nucleus and activates target gene transcription. Activating mutations make this signalling constitutive. FLT3 is mutated in AML; BCL2 overexpression characterizes follicular lymphoma; PTEN loss activates PI3K/AKT.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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