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Factors involved in CLL pathogenesis and cell survival are disrupted by differentiation of CLL B-cells into antibody-secreting cells

Recent research has shown that chronic lymphocytic leukemia (CLL) B-cells display a strong tendency to differentiate into antibody-secreting cells (ASCs) and thus may be amenable to differentiation therapy. However, the effect of this differentiation on factors associated with CLL pathogenesis has n...

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Autores principales: Ghamlouch, Hussein, Darwiche, Walaa, Hodroge, Ahmed, Ouled-Haddou, Hakim, Dupont, Sébastien, Singh, Amrathlal Rabbind, Guignant, Caroline, Trudel, Stéphanie, Royer, Bruno, Gubler, Brigitte, Marolleau, Jean-Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621905/
https://www.ncbi.nlm.nih.gov/pubmed/26050196
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author Ghamlouch, Hussein
Darwiche, Walaa
Hodroge, Ahmed
Ouled-Haddou, Hakim
Dupont, Sébastien
Singh, Amrathlal Rabbind
Guignant, Caroline
Trudel, Stéphanie
Royer, Bruno
Gubler, Brigitte
Marolleau, Jean-Pierre
author_facet Ghamlouch, Hussein
Darwiche, Walaa
Hodroge, Ahmed
Ouled-Haddou, Hakim
Dupont, Sébastien
Singh, Amrathlal Rabbind
Guignant, Caroline
Trudel, Stéphanie
Royer, Bruno
Gubler, Brigitte
Marolleau, Jean-Pierre
author_sort Ghamlouch, Hussein
collection PubMed
description Recent research has shown that chronic lymphocytic leukemia (CLL) B-cells display a strong tendency to differentiate into antibody-secreting cells (ASCs) and thus may be amenable to differentiation therapy. However, the effect of this differentiation on factors associated with CLL pathogenesis has not been reported. In the present study, purified CLL B-cells were stimulated to differentiate into ASCs by phorbol myristate acetate or CpG oligodeoxynucleotide, in combination with CD40 ligand and cytokines in a two-step, seven-day culture system. We investigated (i) changes in the immunophenotypic, molecular, functional, morphological features associated with terminal differentiation into ASCs, (ii) the expression of factors involved in CLL pathogenesis, and (iii) the expression of pro- and anti-apoptotic proteins in the differentiated cells. Our results show that differentiated CLL B-cells are able to display the transcriptional program of ASCs. Differentiation leads to depletion of the malignant program and deregulation of the apoptosis/survival balance. Analysis of apoptosis and the cell cycle showed that differentiation is associated with low cell viability and a low rate of cell cycle entry. Our findings shed new light on the potential for differentiation therapy as a part of treatment strategies for CLL.
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spelling pubmed-46219052015-12-02 Factors involved in CLL pathogenesis and cell survival are disrupted by differentiation of CLL B-cells into antibody-secreting cells Ghamlouch, Hussein Darwiche, Walaa Hodroge, Ahmed Ouled-Haddou, Hakim Dupont, Sébastien Singh, Amrathlal Rabbind Guignant, Caroline Trudel, Stéphanie Royer, Bruno Gubler, Brigitte Marolleau, Jean-Pierre Oncotarget Research Paper Recent research has shown that chronic lymphocytic leukemia (CLL) B-cells display a strong tendency to differentiate into antibody-secreting cells (ASCs) and thus may be amenable to differentiation therapy. However, the effect of this differentiation on factors associated with CLL pathogenesis has not been reported. In the present study, purified CLL B-cells were stimulated to differentiate into ASCs by phorbol myristate acetate or CpG oligodeoxynucleotide, in combination with CD40 ligand and cytokines in a two-step, seven-day culture system. We investigated (i) changes in the immunophenotypic, molecular, functional, morphological features associated with terminal differentiation into ASCs, (ii) the expression of factors involved in CLL pathogenesis, and (iii) the expression of pro- and anti-apoptotic proteins in the differentiated cells. Our results show that differentiated CLL B-cells are able to display the transcriptional program of ASCs. Differentiation leads to depletion of the malignant program and deregulation of the apoptosis/survival balance. Analysis of apoptosis and the cell cycle showed that differentiation is associated with low cell viability and a low rate of cell cycle entry. Our findings shed new light on the potential for differentiation therapy as a part of treatment strategies for CLL. Impact Journals LLC 2015-05-11 /pmc/articles/PMC4621905/ /pubmed/26050196 Text en Copyright: © 2015 Ghamlouch et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Ghamlouch, Hussein
Darwiche, Walaa
Hodroge, Ahmed
Ouled-Haddou, Hakim
Dupont, Sébastien
Singh, Amrathlal Rabbind
Guignant, Caroline
Trudel, Stéphanie
Royer, Bruno
Gubler, Brigitte
Marolleau, Jean-Pierre
Factors involved in CLL pathogenesis and cell survival are disrupted by differentiation of CLL B-cells into antibody-secreting cells
title Factors involved in CLL pathogenesis and cell survival are disrupted by differentiation of CLL B-cells into antibody-secreting cells
title_full Factors involved in CLL pathogenesis and cell survival are disrupted by differentiation of CLL B-cells into antibody-secreting cells
title_fullStr Factors involved in CLL pathogenesis and cell survival are disrupted by differentiation of CLL B-cells into antibody-secreting cells
title_full_unstemmed Factors involved in CLL pathogenesis and cell survival are disrupted by differentiation of CLL B-cells into antibody-secreting cells
title_short Factors involved in CLL pathogenesis and cell survival are disrupted by differentiation of CLL B-cells into antibody-secreting cells
title_sort factors involved in cll pathogenesis and cell survival are disrupted by differentiation of cll b-cells into antibody-secreting cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621905/
https://www.ncbi.nlm.nih.gov/pubmed/26050196
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