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Title: Mutant nucleophosmin deregulates cell death and myeloid differentiation through excessive caspase-6 and -8 inhibition
Authors: Leong, S.M. 
Tan, B.X.
Ahmad, B.B. 
Yan, T.
Chee, L.Y.
Ang, S.T.
Tay, K.G. 
Koh, L.P.
Yeoh, A.E.J.
Koay, E.S.-C.
Mok, Y.-K. 
Lim, T.M. 
Issue Date: 28-Oct-2010
Citation: Leong, S.M., Tan, B.X., Ahmad, B.B., Yan, T., Chee, L.Y., Ang, S.T., Tay, K.G., Koh, L.P., Yeoh, A.E.J., Koay, E.S.-C., Mok, Y.-K., Lim, T.M. (2010-10-28). Mutant nucleophosmin deregulates cell death and myeloid differentiation through excessive caspase-6 and -8 inhibition. Blood 116 (17) : 3286-3296. ScholarBank@NUS Repository.
Abstract: In up to one-third of patients with acute myeloid leukemia, a C-terminal frame-shift mutation results in abnormal and abundant cytoplasmic accumulation of the usually nucleoli-bound protein nucleophosmin (NPM), and this is thought to function in cancer pathogenesis. Here, we demonstrate a gain-of-function role for cytoplasmic NPM in the inhibition of caspase signaling. The NPM mutant specifically inhibits the activities of the cell-death proteases, caspase-6 and -8, through direct interaction with their cleaved, active forms, but not the immature procaspases. The cytoplasmic NPM mutant not only affords protection from death ligand-induced cell death but also suppresses caspase-6/-8-mediated myeloid differentiation. Our data hence provide a potential explanation for the myeloid-specific involvement of cytoplasmic NPM in the leukemogenesis of a large subset of acute myeloid leukemia. © 2010 by The American Society of Hematology.
Source Title: Blood
ISSN: 00064971
DOI: 10.1182/blood-2009-12-256149
Appears in Collections:Staff Publications

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