title: Prognostic significance of NOTCH1 and FBXW7 mutations in pediatric T-ALL.
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. NOTCH1 and FBXW7 mutations both lead the activation of the NOTCH1 pathway and are found in the majority of T-ALL patients. In this study, the mutation analysis of NOTCH1 and FBXW7 genes was performed in 87 pediatric T-ALLs who were treated on the ALL-BFM protocols. In 19 patients (22%), activating NOTCH1 mutations were observed either in the heterodimerization domain or in the PEST domain and 7 cases (10%) demonstrated FBXW7 mutations (2 cases had both NOTCH1 and FBXW7 mutations). We also analyzed the relationship of the mutation data between the clinical and biological data of the patients. NOTCH1 and FBXW7, NOTCH1 alone were found correlated with lower initial leucocyte counts which was independent from the sex and T- cell immunophenotype. However, NOTCH1 and FBXW7 mutations were not predictive of outcome in the overall cohort of pediatric T-ALLs.
authors.affiliation: Institute of Experimental Medicine, Department of Genetics, Istanbul University, Istanbul, Turkey.
authors.forename: Yucel
authors.initials: Y
authors.lastname: Erbilgin
authors.forename: Muge
authors.initials: M
authors.lastname: Sayitoglu
authors.forename: Ozden
authors.initials: O
authors.lastname: Hatirnaz
authors.forename: Omer
authors.initials: O
authors.lastname: Dogru
authors.forename: Arzu
authors.initials: A
authors.lastname: Akcay
authors.forename: Gulen
authors.initials: G
authors.lastname: Tuysuz
authors.forename: Tiraje
authors.initials: T
authors.lastname: Celkan
authors.forename: Gonul
authors.initials: G
authors.lastname: Aydogan
authors.forename: Zafer
authors.initials: Z
authors.lastname: Salcioglu
authors.forename: Cetin
authors.initials: C
authors.lastname: Timur
authors.forename: Lebriz
authors.initials: L
authors.lastname: Yuksel-Soycan
authors.forename: Umit
authors.initials: U
authors.lastname: Ure
authors.forename: Sema
authors.initials: S
authors.lastname: Anak
authors.forename: Leyla
authors.initials: L
authors.lastname: Agaoglu
authors.forename: Omer
authors.initials: O
authors.lastname: Devecioglu
authors.forename: Inci
authors.initials: I
authors.lastname: Yildiz
authors.forename: Ugur
authors.initials: U
authors.lastname: Ozbek
mesh_terms: D000293:Adolescent; D018797:Cell Cycle Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D044783:F-Box Proteins / Q000235:genetics*; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm; D051881:Receptor, Notch1 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; C497761:NOTCH1 protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D051881:Receptor, Notch1; D044767:Ubiquitin-Protein Ligases