GSBS Student Publications

Title

Activating Notch1 mutations in mouse models of T-ALL

Publication Date

2005-09-17

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cancer Biology; Department of Molecular Genetics and Microbiology

Document Type

Article

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Recent studies have demonstrated that most patients with T-cell acute lymphocytic leukemia (T-ALL) have activating mutations in NOTCH1. We sought to determine whether these mutations are also acquired in mouse models of T-ALL. We sequenced the heterodimerization domain and the PEST domain of Notch1 in our mouse model of TAL1-induced leukemia and found that 74% of the tumors harbor activating mutations in Notch1. Cell lines derived from these tumors undergo G(0)/G(1) arrest and apoptosis when treated with a gamma-secretase inhibitor. In addition, we found activating Notch1 mutations in 31% of thymic lymphomas that occur in mice deficient for various combinations of the H2AX, Tp53, and Rag2 genes. Thus, Notch1 mutations are often acquired as a part of the molecular pathogenesis of T-ALLs that develop in mice with known predisposing genetic alterations.

DOI of Published Version

10.1182/blood-2005-06-2553

Source

Blood. 2006 Jan 15;107(2):781-5. Epub 2005 Sep 15. Link to article on publisher's site

Journal/Book/Conference Title

Blood

Related Resources

Link to article in PubMed

PubMed ID

16166587

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