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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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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. |
format | Online Article Text |
id | pubmed-4621905 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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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