Clinical Value of NOTCH1 Mutations Detection among Chronic Lymphocytic Leukemia Patients
Autor: | Salah Aref, Osama Salama, Tarek Abouzeid, Mohamed Sabry, Mohamed El Agder |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Adult Male Chronic lymphocytic leukemia Cohort Studies 03 medical and health sciences symbols.namesake Exon 0302 clinical medicine NOTCH1 hemic and lymphatic diseases Antineoplastic Combined Chemotherapy Protocols medicine Biomarkers Tumor Humans Progression-free survival Receptor Notch1 Aged Sanger sequencing Aged 80 and over business.industry Point mutation Wild type General Medicine Middle Aged medicine.disease mutations Prognosis Leukemia Lymphocytic Chronic B-Cell Survival Rate Leukemia 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Mutation Cancer research symbols Egypt Female Bone marrow business CLL Research Article Follow-Up Studies |
Zdroj: | Asian Pacific Journal of Cancer Prevention : APJCP |
ISSN: | 2476-762X 1513-7368 |
Popis: | Background: The data about the clinical impact of NOTCH1 mutations among Egyptians B – cell chronic lymphocytic patients is not previously identified. We herein, evaluate the prevalence and the prognostic significance of neurogenic locus notch homolog protein-1 (NOTCH1) mutations in B- cell lymphocytic leukemia (B-CLL). Methods: A cohort of 105 Egyptian B-CLL patients aging from 43 to 86 years. PCR products including NOTCH1 exon 26, 27, and distal part of exon 34 expanding the sequences encoding transcription activation domain (TAD) and a peptide sequence rich in proline (P), glutamic acid (E), serine (S), threonine (T) (PEST domains) were sequenced by direct DNA Sanger sequencing. Results: NOTCH1 mutations were detected in 48/105 of patients (45.7%). Mutations in B-CLL patients are insertions (n=21), point mutations (n=18) and deletions (n=12). NOTCH1 mutations showed significant impact on prognosis of B-CLL patients as they were associated with increased bone marrow lymphocytes, more relapse and high incidence of mortality, shortened overall survival and progression free survival, and lymphocytes doubling time, when compared with NOTCH1 wild type B-CLL patients (P= 0.001; 0,005; 0.042; 0.049; 0.008; 0.049 respectively). Conclusion: NOTCH1 mutations were considered as bad prognostic marker in B-CLL and suggested to be included in risk stratification of B-CLL patients at diagnosis. |
Databáze: | OpenAIRE |
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