Document Detail


High expression of AID and active class switch recombination might account for a more aggressive disease in unmutated CLL patients: link with an activated microenvironment in CLL disease.
MedLine Citation:
PMID:  20233972     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Interaction of chronic lymphocytic leukemia (CLL) B cells with tissue microenvironment has been suggested to favor disease progression by promoting malignant B-cell growth. Previous work has shown expression in peripheral blood (PB) of CLL B cells of activation-induced cytidine deaminase (AID) among CLL patients with an unmutated (UM) profile of immunoglobulin genes and with ongoing class switch recombination (CSR) process. Because AID expression results from interaction with activated tissue microenvironment, we speculated whether the small subset with ongoing CSR is responsible for high levels of AID expression and could be derived from this particular microenvironment. In this work, we quantified AID expression and ongoing CSR in PB of 50 CLL patients and characterized the expression of different molecules related to microenvironment interaction. Our results show that among UM patients (1) high AID expression is restricted to the subpopulation of tumoral cells ongoing CSR; (2) this small subset expresses high levels of proliferation, antiapoptotic and progression markers (Ki-67, c-myc, Bcl-2, CD49d, and CCL3/4 chemokines). Overall, this work outlines the importance of a cellular subset in PB of UM CLL patients with a poor clinical outcome, high AID levels, and ongoing CSR, whose presence might be a hallmark of a recent contact with the microenvironment.
Authors:
Florencia Palacios; Pilar Moreno; Pablo Morande; Cecilia Abreu; Agust?n Correa; Valentina Porro; Ana Ines Landoni; Raul Gabus; Mirta Giordano; Guillermo Dighiero; Otto Pritsch; Pablo Oppezzo
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-16
Journal Detail:
Title:  Blood     Volume:  115     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-04     Completed Date:  2010-06-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4488-96     Citation Subset:  AIM; IM    
Affiliation:
Unit of Recombinant Protein, Institut Pasteur de Montevideo, Montevideo, Uruguay.
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MeSH Terms
Descriptor/Qualifier:
B-Lymphocyte Subsets / enzymology,  immunology,  pathology
Base Sequence
Cell Proliferation
Cytidine Deaminase / blood*,  genetics*
DNA Primers / genetics
Gene Expression
Humans
Immunoglobulin Class Switching*
Leukemia, Lymphocytic, Chronic, B-Cell / enzymology*,  genetics*,  immunology
Mutation
Prognosis
RNA, Messenger / blood,  genetics
RNA, Neoplasm / blood,  genetics
Tumor Markers, Biological / genetics
Chemical
Reg. No./Substance:
0/DNA Primers; 0/RNA, Messenger; 0/RNA, Neoplasm; 0/Tumor Markers, Biological; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/Cytidine Deaminase

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