Abstract
BACKGROUND: Acute Lymphoblastic Leukemia (ALL) is a prevalent childhood malignancy characterized by abnormal lymphoid cell proliferation. Despite treatment advancements, relapse remains problematic, necessitating improved prognostic markers. NOTCH1 mutations, particularly in T-cell ALL (T-ALL), have been implicated in ALL pathogenesis. METHODS: We examined the correlation between NOTCH1 mutations and clinical characteristics in 185 Indian pediatric ALL patients. NOTCH1 mutations were detected using PCR and sequencing, with subsequent analysis of clinical parameters and outcomes. RESULTS: Twenty-four cases exhibited NOTCH1 mutations, primarily in the PEST domain, with a higher frequency in B-cell ALL (B-ALL) than in T-ALL. Specific clinical features, including elevated WBC counts and LDH levels, were associated with NOTCH1 mutations. Survival analysis suggested potential prognostic implications of NOTCH1 mutations in B-ALL but not in T-ALL. Integrating NOTCH1 mutation status with minimal residual disease levels post-induction therapy may aid in identifying high-risk patients. CONCLUSIONS: Our findings underscore the heterogeneous nature of ALL and advocate for personalized therapy guided by molecular markers. Further research is essential to elucidate the role of NOTCH1 mutations in ALL prognosis and treatment response.