Document Detail

Molecular pathogenesis of chronic lymphocytic leukemia.
MedLine Citation:
PMID:  23023714     Owner:  NLM     Status:  MEDLINE    
Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Here, we highlight important genetic alterations that contribute to tumorigenesis, clinical progression, and chemorefractoriness of CLL. All CLLs share a common gene expression profile that suggests derivation from antigen-experienced B cells, a model supported by frequent B cell receptor repertoire skewing and stereotypy. Many CLL patients carry mutated immuno-globulin heavy-chain variable genes, while approximately 35% harbor unmutated IgV genes, which are associated with an inferior outcome. Deletion of chromosome 13q14, which is the most common genetic mutation at diagnosis, is considered an initiating lesion that frequently results in disruption of the tumor suppressor locus DLEU2/MIR15A/MIR16A. Next-generation sequencing has revealed additional recurrent genetic lesions that are implicated in CLL pathogenesis. These advancements in the molecular genetics of CLL have important implications for stratifying treatment based on molecular prognosticators and for targeted therapy.
Gianluca Gaidano; Robin Foà; Riccardo Dalla-Favera
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2012-10-01
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  122     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-01     Completed Date:  2013-02-01     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3432-8     Citation Subset:  AIM; IM    
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MeSH Terms
Antigens / immunology
B-Lymphocytes / immunology,  pathology
Cell Lineage
Cell Transformation, Neoplastic
Chromosome Aberrations
Disease Progression
Gene Expression Profiling
Genes, Immunoglobulin
Genes, Tumor Suppressor
Immunoglobulin Heavy Chains / genetics
Immunoglobulin Variable Region / genetics
Leukemia, Experimental / genetics,  immunology
Leukemia, Lymphocytic, Chronic, B-Cell / etiology,  genetics*,  pathology
Mice, Transgenic
Neoplasm Proteins / genetics,  physiology
Neoplastic Stem Cells / immunology,  pathology
Somatic Hypermutation, Immunoglobulin
Tumor Suppressor Proteins / genetics
Reg. No./Substance:
0/Antigens; 0/DLEU2 protein, human; 0/Immunoglobulin Heavy Chains; 0/Immunoglobulin Variable Region; 0/Neoplasm Proteins; 0/Tumor Suppressor Proteins

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