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Leuk Res. 2007 Mar;31(3):321-7. Epub 2006 Jul 25.

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

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1
Department of Medicine, Columbia University, New York, NY 10032, USA.

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.

PMID:
16870249
DOI:
10.1016/j.leukres.2006.06.009
[Indexed for MEDLINE]

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