Abstract
The NOTCH signaling pathway plays important role in the development of multicellular organisms, as it regulates cell proliferation, survival, and differentiation. In adults, it is essential for the T- or B-lymphocyte lineage commitment.NOTCH1and FBXW7 mutations both lead the activation of theNOTCH1pathway and are found in the majority of T-ALL patients. In this study, the mutation analysis ofNOTCH1andFBXW7genes was performed in 87 pediatric T-ALLs who were treated on the ALL-BFM protocols. In 19 patients (22%), activatingNOTCH1mutations were observed either in the heterodimerization domain or in the PEST domain and 7 cases (10%) demonstrated FBXW7 mutations (2 cases had bothNOTCH1andFBXW7mutations). We also analyzed the relationship of the mutation data between the clinical and biological data of the patients.NOTCH1andFBXW7,NOTCH1alone were found correlated with lower initial leucocyte counts which was independent from the sex and T- cell immunophenotype. However,NOTCH1andFBXW7mutations were not predictive of outcome in the overall cohort of pediatric T-ALLs.
Highlights
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes, generally characterized by very high circulating blast cell counts, mediastinal masses and central nervous system involvement [1,2]
A total of 87 T-ALL patients were analyzed for NOTCH1 gene mutations
We found 10% FBXW7 mutations and 22,2% NOTCH1 mutations in T-ALL patients
Summary
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes, generally characterized by very high circulating blast cell counts, mediastinal masses and central nervous system involvement [1,2]. It affects both children and adults and is rapidly fatal [3]. Malign transformation of T-cell is caused by chromosomal translocation and other genetic, epigenetic abnormalities which lead to loss of cell-cycle control, unlimited self-renewal capacity, impaired differentiation and increased blastic cell proliferation [8]. Less than 1% of T-ALL shelter chromosomal translocation t(7;9) (q34;q34.3) involves NOTCH1 [9].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
