Document Detail


IGHV unmutated CLL B cells are more prone to spontaneous apoptosis and subject to environmental prosurvival signals than mutated CLL B cells.
MedLine Citation:
PMID:  21372840     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-03-04
Journal Detail:
Title:  Leukemia     Volume:  25     ISSN:  1476-5551     ISO Abbreviation:  Leukemia     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-11     Completed Date:  2011-08-09     Revised Date:  2013-03-04    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  England    
Other Details:
Languages:  eng     Pagination:  828-37     Citation Subset:  IM    
Affiliation:
Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliero Universitaria San Giovanni Battista di Torino, Torino, Italy. marta.coscia@unito.it
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MeSH Terms
Descriptor/Qualifier:
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:
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

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