الفهرس 
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Abstract
Aim of the work: This study aimed to determine the prevalence of NOTCH1 mutations among patients with lymphoid leukemias, as well as, it’s relation to disease behavior and patient outcome. Patient and method: A cohort of 15 T-ALL and 35 CLL Egyptian cases. Age of CLL cases ranged from 43 to 86 years old. But T-ALL cases was ranging from 5-66 years. Samples were investigated by direct DNA Sanger sequencing of PCR products including NOTCH1 exon 26, 27, and distal part of exon 34 expanding the sequences encoding TAD and PEST domains. Results: NOTCH1 mutations was detected in 10 out of 15 T ALL patients (66%) and 16 out of 35 CLL patients (45.7%). Mutations in T-ALL patients are point mutation or deletion but in CLL patients there is also insertional mutations. NOTCH1 mutations was found to have significant impact on clinical outcome and prognosis in CLL patients. As we found that CLL patients with NOTCH1 mutations were associated with increased bone marrow lymphocytes, shortened overall survival, progression free survival, and lymphocytes doubling time, more relapse and mortality as compared with NOTCH1 wild type CLL patients. On the other hand, no statistically significant prognostic impact in T-ALL patients. Conclusion: NOTCH1 mutations is considered as bad prognostic marker in CLL but not in T-ALL patients and could be used for risk stratification at diagnosis in CLL patients.