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Publication : Activating Notch1 mutations are an early event in T-cell malignancy of Ikaros point mutant Plastic/+ mice.

First Author  Mantha S Year  2007
Journal  Leuk Res Volume  31
Issue  3 Pages  321-7
PubMed ID  16870249 Mgi Jnum  J:120630
Mgi Id  MGI:3707311 Doi  10.1016/j.leukres.2006.06.009
Citation  Mantha S, et al. (2007) Activating Notch1 mutations are an early event in T-cell malignancy of Ikaros point mutant Plastic/+ mice. Leuk Res 31(3):321-7
abstractText  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.
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