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Science. 2004 Oct 8;306(5694):269-71.

Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia.

Author information

1
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Abstract

Very rare cases of human T cell acute lymphoblastic leukemia (T-ALL) harbor chromosomal translocations that involve NOTCH1, a gene encoding a transmembrane receptor that regulates normal T cell development. Here, we report that more than 50% of human T-ALLs, including tumors from all major molecular oncogenic subtypes, have activating mutations that involve the extracellular heterodimerization domain and/or the C-terminal PEST domain of NOTCH1. These findings greatly expand the role of activated NOTCH1 in the molecular pathogenesis of human T-ALL and provide a strong rationale for targeted therapies that interfere with NOTCH signaling.

PMID:
15472075
DOI:
10.1126/science.1102160
[Indexed for MEDLINE]
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