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Annals of Hematology
Published in: Annals of Hematology 2/2014

01-02-2014 | Original Article

Arsenic trioxide suppressed mantle cell lymphoma by downregulation of cyclin D1

Authors: Rico K. H. Lo, Yok-Lam Kwong

Published in: Annals of Hematology | Issue 2/2014

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Abstract

Mantle cell lymphoma (MCL) is aggressive with poor prognosis. Due to t(11;14)(q13;q32), cyclin D1 is overexpressed. The in vitro activities of arsenic trioxide (As2O3) in MCL were investigated. In MCL lines Jeko-1 and Granta-519, As2O3 induced dose-dependent and time-dependent increases in apoptosis accompanied by cyclin D1 suppression. Downregulation of cyclin D1 resulted in decreased retinoblastoma protein phosphorylation, which led to repressed G1 progression to S/G2 phases. As2O3 did not affect cyclin D1 gene transcription. Instead, As2O3 activated glycogen synthase kinase-3beta (by tyrosine-216 phosphorylation) and IkappaB kinase alpha/beta (by serine-176/180 phosphorylation), both of which phosphorylated cyclin D1 at threonine-286, leading to its poly-ubiquitination and degradation in the proteasome. These observations were recapitulated partly in primary MCL samples obtained from patients refractory to conventional treatment. Our findings suggested that As2O3 might be clinically useful in MCL.
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Metadata
Title
Arsenic trioxide suppressed mantle cell lymphoma by downregulation of cyclin D1
Authors
Rico K. H. Lo
Yok-Lam Kwong
Publication date
01-02-2014
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 2/2014
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-013-1866-2

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