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• W2024860689 abstract "Abstract Purpose: Activating Notch-1 mutations are frequent in T-cell acute lymphoblastic leukemia (T-ALL), occurring in &gt;50% of patients. In murine models of T-ALL, Notch-1 activation can both directly initiate leukemia and cooperate secondarily to other primary events. Whether acquisition of Notch-1 mutations is an early initiating event or a secondary event in the pathogenesis of human T-ALL is unclear. Experimental Design: We used denaturing high-performance liquid chromatography, sequencing, and fragment analysis to analyze Notch-1 mutational status and mutant level in 62 patients at presentation as well as 16 matched presentation-relapse samples. Results: We detected Notch-1 mutations in 47 patients (76%). Seven of these were low-level mutations (quantified at ≤10%), despite high blast counts, suggesting that they were acquired as a secondary event in a subclone. Of 16 matched presentation-relapse samples studied, 7 were wild-type at both presentation and relapse. Five of nine mutant-positive patients at presentation relapsed with the same mutation(s) at the same high level. Four patients had evidence of a change in mutant at relapse. One lost a PEST mutation and became wild-type. Two others lost mutations at relapse but acquired different mutations, despite unchanged T-cell receptor rearrangements, suggesting that the latter event predated the acquisition of the Notch-1 mutation. One relapsed with a secondary T-cell leukemia and different Notch mutation. Conclusions: These results suggest that Notch-1 mutations can sometimes be acquired as secondary events in leukemogenesis and must be used cautiously as solitary minimal residual disease markers." @default.
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• W2024860689 date "2007-12-01" @default.
• W2024860689 modified "2023-10-07" @default.
• W2024860689 title "Notch-1 Mutations Are Secondary Events in Some Patients with T-Cell Acute Lymphoblastic Leukemia" @default.
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• W2024860689 doi "https://doi.org/10.1158/1078-0432.ccr-07-1474" @default.
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