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Title of Journal: Int J Hematol

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Abbravation: International Journal of Hematology

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Springer Japan

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DOI

10.1016/j.aquaeng.2004.01.003

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1865-3774

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Critical roles of NOTCH1 in acute Tcell lymphobla

Authors: Hudan Liu Mark Y Chiang Warren S Pear
Publish Date: 2011/08/05
Volume: 94, Issue: 2, Pages: 118-125
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Abstract

NOTCH1 plays a central role in Tcell development and when aberrantly activated in acute Tcell lymphoblastic leukemia TALL As a transmembrane receptor that is ultimately converted into a transcription factor NOTCH1 directly activates a spectrum of target genes which function to mediate NOTCH1 signaling in normal or transformed T cells During physiologic Tcell development NOTCH1 has important functions in cell fate determination proliferation survival and metabolism Activating NOTCH1 mutations occur in more than half of human patients with TALL suggesting an important role for aberrant NOTCH1 signaling in the pathogenesis of this disease Inhibiting NOTCH1 signaling in patientderived cell lines and murine TALLs leads to growth arrest and/or apoptosis suggesting that NOTCH1 inhibitors can improve TALL treatment However there are challenges to translate NOTCH1 inhibitors to the clinic because of toxicity and resistance This review focuses on molecular mechanisms of oncogenic NOTCH1 signaling molecular and functional analysis of NOTCH1 transcriptional targets in TALL and recent advances in therapeutic targeting of NOTCH1This work was supported by grants from the National Institute of Health to WSP R01AI047833 P01CA119070 and a Leukemia and Lymphoma Society SCOR Award to WSP HL was provided with an NIHfunded Institutional Research Training Grant T32DK07780 and a Fellow Award from the Lymphoma Research Foundation MYC received a career development award from the NCI K08 CA12054401

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