Background: Molecular alterations occur frequently in T-ALL and the potential impact of those abnormalities on\r\noutcome is still controversial. The current study aimed to test whether NOTCH1 mutations and additional molecular\r\nabnormalities would impact T-ALL outcome in a series of 138 T-ALL paediatric cases.\r\nMethods: T-ALL subtypes, status of SIL-TAL1 fusion, ectopic expression of TLX3, and mutations in FBXW7, KRAS,\r\nPTEN and NOTCH1 were assessed as overall survival (OS) and event-free survival (EFS) prognostic factors. OS and\r\nEFS were determined using the Kaplan-Meier method and compared using the log-rank test.\r\nResults: The frequencies of mutations were 43.5% for NOTCH1, while FBXW7, KRAS and PTEN exhibited frequencies\r\nof 19.1%, 9.5% and 9.4%, respectively. In 78.3% of cases, the coexistence of NOTCH1 mutations and other molecular\r\nalterations was observed. In multivariate analysis no statistical association was revealed between NOTCH1 mutations\r\nand any other variable analyzed. The mean length of the follow-up was 68.4 months and the OS was 50.7%. SILTAL1\r\nwas identified as an adverse prognostic factor. NOTCH1 mutation status was not associated with outcome,\r\nwhile the presence of NOTCH1 complex mutations (indels) were associated with a longer overall survival (p =\r\n0.031) than point mutations.\r\nConclusion: NOTCH1 mutations alone or in combination with FBXW7 did not impact T-ALL prognosis.\r\nNevertheless, complex NOTCH1 mutations appear to have a positive impact on OS and the SIL-TAL1 fusion was\r\nvalidated as a negative prognostic marker in our series of T-ALL.
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