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Annals of Hematology

Erschienen in:

01.02.2014 | Original Article

Arsenic trioxide suppressed mantle cell lymphoma by downregulation of cyclin D1

verfasst von: Rico K. H. Lo, Yok-Lam Kwong

Erschienen in: Annals of Hematology | Ausgabe 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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Titel: Arsenic trioxide suppressed mantle cell lymphoma by downregulation of cyclin D1
verfasst von: Rico K. H. Lo
Yok-Lam Kwong
Publikationsdatum: 01.02.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: Annals of Hematology / Ausgabe 2/2014
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-013-1866-2

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