ABERRANT NOTCH SIGNALING IN ACUTE LEUKEMIA

Notch signaling influences cellular proliferation, differentiation and apoptosis in diverse biological processes. Consistent with diverse effects of Notch signaling in multiple tissues, abnormalities of Notch pathway molecules are associated with malignant neoplasms. In humans, these include gain-of...

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Bibliographic Details
Published in:Anticancer research 2008-10, Vol.28 (5C)
Main Authors: Suzukawa, K, Nemoto, N, Chiba, S
Format: Article
Language:English
Online Access:Get full text
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Summary:Notch signaling influences cellular proliferation, differentiation and apoptosis in diverse biological processes. Consistent with diverse effects of Notch signaling in multiple tissues, abnormalities of Notch pathway molecules are associated with malignant neoplasms. In humans, these include gain-of-function mutations of NOTCH1, the gene for a receptor, and loss-of-function mutations of FBW7, the gene for an E3 ubiquitin ligase, in T-cell acute lymphoblastic leukemias (T-ALL), and generation of a fusion gene involving a chromatin regulator gene MLL and a Notch-specific coativator gene, mastermind like-2 (MAML2; MLL-MAML2), in T-ALL as well as acute myeloid leukemias. Results of luciferase assay revealed that the MLL-MAML2 fusion gene caused aberrant Notch signaling. Interestingly, MLL-MAML2 conferred interleukin-3 (IL-3)-independent growth on cells that were originally dependent on IL-3 through the activation of IL-3 gene transcription. Activation of an autocrine cytokine circuit might be one of the mechanisms of leukemogenesis by MLL-MAML2.
ISSN:0250-7005