title: Activating Notch1 mutations are an early event in T-cell malignancy of Ikaros point mutant Plastic/+ mice.
abstract: Ikaros and Notch1 genes are critical to T-cell differentiation through transcriptional activation of target genes and interaction with chromatin remodeling complexes. An Ikaros (Plastic) point mutation inhibits activity of normal Ikaros and Ikaros family members, and leads to T-cell lymphoma in heterozygotes (Plstc/+). Analysis revealed Notch1 activating mutations in 12 of 17 Plstc/+ lymphomas (70%), analogous to those in human T-ALL. Mice acquired Notch1 mutations in lymph nodes as early as 7 weeks. Thus, combined Notch1 and Ikaros dysfunction can be a significant early event in T-cell proliferation and tumorigenesis.
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Mantha
authors.forename: Maureen
authors.initials: M
authors.lastname: Ward
authors.forename: Jonathan
authors.initials: J
authors.lastname: McCafferty
authors.forename: Alan
authors.initials: A
authors.lastname: Herron
authors.forename: Teresa
authors.initials: T
authors.lastname: Palomero
authors.forename: Adolfo
authors.initials: A
authors.lastname: Ferrando
authors.forename: Arthur
authors.initials: A
authors.lastname: Bank
authors.forename: Christine
authors.initials: C
authors.lastname: Richardson
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006579:Heterozygote; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics* / Q000276:immunology; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017354:Point Mutation; D051881:Receptor, Notch1 / Q000235:genetics* / Q000276:immunology; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor