A combination of cytokines rescues highly purified leukemic CLL B-cells from spontaneous apoptosis in vitro.
B-chronic lymphocytic leukemia (B-CLL), the most common human leukemia, is characterized by predominantly non-dividing malignant mature CD5+ B lymphocytes with an apoptosis defect. Various microenvironmental stimuli confer a growth advantage on these leukemic cells and extend their survival in vivo....
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3608602?pdf=render |
| _version_ | 1811233606560907264 |
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| author | Hussein Ghamlouch Hakim Ouled-Haddou Gandhi Damaj Bruno Royer Brigitte Gubler Jean-Pierre Marolleau |
| author_facet | Hussein Ghamlouch Hakim Ouled-Haddou Gandhi Damaj Bruno Royer Brigitte Gubler Jean-Pierre Marolleau |
| author_sort | Hussein Ghamlouch |
| collection | DOAJ |
| description | B-chronic lymphocytic leukemia (B-CLL), the most common human leukemia, is characterized by predominantly non-dividing malignant mature CD5+ B lymphocytes with an apoptosis defect. Various microenvironmental stimuli confer a growth advantage on these leukemic cells and extend their survival in vivo. Nevertheless, when cultured in vitro, CLL B-cells rapidly die from apoptosis. Certain cytokines may extend the survival capacity of CLL B-cells in vitro and individual anti-apoptotic effects of several cytokines have been reported. The potential cumulative effect of such cytokines has not been studied. We therefore investigated the effects on CLL B-cells survival in vitro of humoral factors, polyclonal lymphocyte activators and a combination of cytokines known for their anti-apoptotic effects. Purified CLL B-cells were cultured in the presence or absence of various soluble molecules and the leukemic cell response was assessed in terms of viability. Apoptotic cell death was detected by flow cytometry using annexinV and 7-amino-actinomycin. The survival of CLL B-cells in vitro was highly variable. When tested separately, cytokines (IL-2, -6, -10, -12, -15, -21, BAFF and APRIL) improved CLL B cell survival moderately; in combination, they significantly enhanced survival of these cells, even up to 7 days of culture. We also report that humoral factors from autologous serum are important for survival of these malignant cells. Our findings support the concept that the CLL microenvironment is critical and suggest that soluble factors may contribute directly to the prolonged survival of CLL B-cells. Therefore, the combination of cytokines we describe as providing strong resistance to apoptosis in vitro might be used to improve the treatment of CLL. |
| first_indexed | 2024-04-12T11:22:37Z |
| format | Article |
| id | doaj.art-dd77e1d06f0e4b24a2cebb3387257ae6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T11:22:37Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-dd77e1d06f0e4b24a2cebb3387257ae62022-12-22T03:35:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0183e6037010.1371/journal.pone.0060370A combination of cytokines rescues highly purified leukemic CLL B-cells from spontaneous apoptosis in vitro.Hussein GhamlouchHakim Ouled-HaddouGandhi DamajBruno RoyerBrigitte GublerJean-Pierre MarolleauB-chronic lymphocytic leukemia (B-CLL), the most common human leukemia, is characterized by predominantly non-dividing malignant mature CD5+ B lymphocytes with an apoptosis defect. Various microenvironmental stimuli confer a growth advantage on these leukemic cells and extend their survival in vivo. Nevertheless, when cultured in vitro, CLL B-cells rapidly die from apoptosis. Certain cytokines may extend the survival capacity of CLL B-cells in vitro and individual anti-apoptotic effects of several cytokines have been reported. The potential cumulative effect of such cytokines has not been studied. We therefore investigated the effects on CLL B-cells survival in vitro of humoral factors, polyclonal lymphocyte activators and a combination of cytokines known for their anti-apoptotic effects. Purified CLL B-cells were cultured in the presence or absence of various soluble molecules and the leukemic cell response was assessed in terms of viability. Apoptotic cell death was detected by flow cytometry using annexinV and 7-amino-actinomycin. The survival of CLL B-cells in vitro was highly variable. When tested separately, cytokines (IL-2, -6, -10, -12, -15, -21, BAFF and APRIL) improved CLL B cell survival moderately; in combination, they significantly enhanced survival of these cells, even up to 7 days of culture. We also report that humoral factors from autologous serum are important for survival of these malignant cells. Our findings support the concept that the CLL microenvironment is critical and suggest that soluble factors may contribute directly to the prolonged survival of CLL B-cells. Therefore, the combination of cytokines we describe as providing strong resistance to apoptosis in vitro might be used to improve the treatment of CLL.http://europepmc.org/articles/PMC3608602?pdf=render |
| spellingShingle | Hussein Ghamlouch Hakim Ouled-Haddou Gandhi Damaj Bruno Royer Brigitte Gubler Jean-Pierre Marolleau A combination of cytokines rescues highly purified leukemic CLL B-cells from spontaneous apoptosis in vitro. PLoS ONE |
| title | A combination of cytokines rescues highly purified leukemic CLL B-cells from spontaneous apoptosis in vitro. |
| title_full | A combination of cytokines rescues highly purified leukemic CLL B-cells from spontaneous apoptosis in vitro. |
| title_fullStr | A combination of cytokines rescues highly purified leukemic CLL B-cells from spontaneous apoptosis in vitro. |
| title_full_unstemmed | A combination of cytokines rescues highly purified leukemic CLL B-cells from spontaneous apoptosis in vitro. |
| title_short | A combination of cytokines rescues highly purified leukemic CLL B-cells from spontaneous apoptosis in vitro. |
| title_sort | combination of cytokines rescues highly purified leukemic cll b cells from spontaneous apoptosis in vitro |
| url | http://europepmc.org/articles/PMC3608602?pdf=render |
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