| IGHV unmutated CLL B cells are more prone to spontaneous apoptosis and subject to environmental prosurvival signals than mutated CLL B cells. | |
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MedLine Citation:
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PMID: 21372840 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Tumor cells in chronic lymphocytic leukemia (CLL) are more prone to apoptosis when cultured ex vivo, because they lack prosurvival signals furnished in vivo via B-cell receptor (BCR)-dependent and -independent pathways. This study compared the susceptibility of unmutated (UM) and mutated (M) CLL B cells to spontaneous apoptosis and prosurvival signals. UM CLL B cells showed a significantly higher rate of spontaneous apoptosis than M CLL B cells. Nuclear factor-kB (NF-kB) was rapidly inactivated, and B-cell leukemia/lymphoma 2 (Bcl-2) expression progressively down-regulated in the UM CLL B cells. CD40-Ligand, interleukin-4 and stromal cells significantly improved their viability and partially recovered Bcl-2, but not NF-kB expression. Peripheral blood mononuclear cells also offered protection of UM CLL B cells, and recovered both NF-kB and Bcl-2 expression. T cells, rather than nurse-like cells, were responsible for protecting UM CLL B cells by means of cell-to-cell contact and soluble factors. Despite their more aggressive features, UM CLL B cells are more susceptible to spontaneous apoptosis and depend from environmental prosurvival signals. This vulnerability of UM CLL B cells can be exploited as a selective target of therapeutic interventions. |
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Authors:
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M Coscia; F Pantaleoni; C Riganti; C Vitale; M Rigoni; S Peola; B Castella; M Foglietta; V Griggio; D Drandi; M Ladetto; A Bosia; M Boccadoro; M Massaia |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-03-04 |
Journal Detail:
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Title: Leukemia Volume: 25 ISSN: 1476-5551 ISO Abbreviation: Leukemia Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-05-11 Completed Date: 2011-08-09 Revised Date: 2013-03-04 |
Medline Journal Info:
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Nlm Unique ID: 8704895 Medline TA: Leukemia Country: England |
Other Details:
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Languages: eng Pagination: 828-37 Citation Subset: IM |
Affiliation:
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Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliero Universitaria San Giovanni Battista di Torino, Torino, Italy. marta.coscia@unito.it |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aged, 80 and over Apoptosis* B-Lymphocytes / metabolism, pathology* Blotting, Western CD40 Ligand / metabolism Electrophoretic Mobility Shift Assay Female Humans Immunoglobulin Heavy Chains / genetics* Immunoglobulin Variable Region / genetics* Leukemia, Lymphocytic, Chronic, B-Cell / genetics*, immunology, pathology* Male Middle Aged Mutation / genetics* NF-kappa B / genetics, metabolism Proto-Oncogene Proteins c-bcl-2 / metabolism Receptors, Antigen, B-Cell / metabolism Signal Transduction Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Immunoglobulin Heavy Chains; 0/Immunoglobulin Variable Region; 0/NF-kappa B; 0/Proto-Oncogene Proteins c-bcl-2; 0/Receptors, Antigen, B-Cell; 147205-72-9/CD40 Ligand |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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