Inhibition of DEPDC1A, a bad prognostic marker in multiple myeloma, delays growth and induces mature plasma cell markers in malignant plasma cells.

High throughput DNA microarray has made it possible to outline genes whose expression in malignant plasma cells is associated with short overall survival of patients with Multiple Myeloma (MM). A further step is to elucidate the mechanisms encoded by these genes yielding to drug resistance and/or pa...

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Autores principales: Alboukadel Kassambara, Matthieu Schoenhals, Jérôme Moreaux, Jean-Luc Veyrune, Thierry Rème, Hartmut Goldschmidt, Dirk Hose, Bernard Klein
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/508612106bfa427fa972fa82872ef90a
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spelling oai:doaj.org-article:508612106bfa427fa972fa82872ef90a2021-11-18T07:47:23ZInhibition of DEPDC1A, a bad prognostic marker in multiple myeloma, delays growth and induces mature plasma cell markers in malignant plasma cells.1932-620310.1371/journal.pone.0062752https://doaj.org/article/508612106bfa427fa972fa82872ef90a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23646139/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203High throughput DNA microarray has made it possible to outline genes whose expression in malignant plasma cells is associated with short overall survival of patients with Multiple Myeloma (MM). A further step is to elucidate the mechanisms encoded by these genes yielding to drug resistance and/or patients' short survival. We focus here on the biological role of the DEP (for Disheveled, EGL-10, Pleckstrin) domain contained protein 1A (DEPDC1A), a poorly known protein encoded by DEPDC1A gene, whose high expression in malignant plasma cells is associated with short survival of patients. Using conditional lentiviral vector delivery of DEPDC1A shRNA, we report that DEPDC1A knockdown delayed the growth of human myeloma cell lines (HMCLs), with a block in G2 phase of the cell cycle, p53 phosphorylation and stabilization, and p21(Cip1) accumulation. DEPDC1A knockdown also resulted in increased expression of mature plasma cell markers, including CXCR4, IL6-R and CD38. Thus DEPDC1A could contribute to the plasmablast features of MMCs found in some patients with adverse prognosis, blocking the differentiation of malignant plasma cells and promoting cell cycle.Alboukadel KassambaraMatthieu SchoenhalsJérôme MoreauxJean-Luc VeyruneThierry RèmeHartmut GoldschmidtDirk HoseBernard KleinPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e62752 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Alboukadel Kassambara
Matthieu Schoenhals
Jérôme Moreaux
Jean-Luc Veyrune
Thierry Rème
Hartmut Goldschmidt
Dirk Hose
Bernard Klein
Inhibition of DEPDC1A, a bad prognostic marker in multiple myeloma, delays growth and induces mature plasma cell markers in malignant plasma cells.
description High throughput DNA microarray has made it possible to outline genes whose expression in malignant plasma cells is associated with short overall survival of patients with Multiple Myeloma (MM). A further step is to elucidate the mechanisms encoded by these genes yielding to drug resistance and/or patients' short survival. We focus here on the biological role of the DEP (for Disheveled, EGL-10, Pleckstrin) domain contained protein 1A (DEPDC1A), a poorly known protein encoded by DEPDC1A gene, whose high expression in malignant plasma cells is associated with short survival of patients. Using conditional lentiviral vector delivery of DEPDC1A shRNA, we report that DEPDC1A knockdown delayed the growth of human myeloma cell lines (HMCLs), with a block in G2 phase of the cell cycle, p53 phosphorylation and stabilization, and p21(Cip1) accumulation. DEPDC1A knockdown also resulted in increased expression of mature plasma cell markers, including CXCR4, IL6-R and CD38. Thus DEPDC1A could contribute to the plasmablast features of MMCs found in some patients with adverse prognosis, blocking the differentiation of malignant plasma cells and promoting cell cycle.
format article
author Alboukadel Kassambara
Matthieu Schoenhals
Jérôme Moreaux
Jean-Luc Veyrune
Thierry Rème
Hartmut Goldschmidt
Dirk Hose
Bernard Klein
author_facet Alboukadel Kassambara
Matthieu Schoenhals
Jérôme Moreaux
Jean-Luc Veyrune
Thierry Rème
Hartmut Goldschmidt
Dirk Hose
Bernard Klein
author_sort Alboukadel Kassambara
title Inhibition of DEPDC1A, a bad prognostic marker in multiple myeloma, delays growth and induces mature plasma cell markers in malignant plasma cells.
title_short Inhibition of DEPDC1A, a bad prognostic marker in multiple myeloma, delays growth and induces mature plasma cell markers in malignant plasma cells.
title_full Inhibition of DEPDC1A, a bad prognostic marker in multiple myeloma, delays growth and induces mature plasma cell markers in malignant plasma cells.
title_fullStr Inhibition of DEPDC1A, a bad prognostic marker in multiple myeloma, delays growth and induces mature plasma cell markers in malignant plasma cells.
title_full_unstemmed Inhibition of DEPDC1A, a bad prognostic marker in multiple myeloma, delays growth and induces mature plasma cell markers in malignant plasma cells.
title_sort inhibition of depdc1a, a bad prognostic marker in multiple myeloma, delays growth and induces mature plasma cell markers in malignant plasma cells.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/508612106bfa427fa972fa82872ef90a
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