Document Detail


Mutated IgHV1-69 gene usage represents a distinct subgroup associated with indolent disease in chronic lymphocytic leukemia.
MedLine Citation:
PMID:  18398745     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Biased IgHV gene usage in chronic lymphocytic leukemia (CLL) is well documented and suggests antigen involvement in leukemogenesis. IgHV1-69 is one of the most frequently rearranged IgHV genes in CLL and the majority of IgHV1-69 cases lack somatic hypermutation and display poor prognosis. However, its independent prognostic impact remains uncertain given reports showing a low proportion of mutated IgHV1-69 cases and stereotyped IgHV1-69 subsets with divergent clinical outcome. We assessed the frequency and clinical significance of IgHV1-69 gene usage in a cohort of 330 CLL patients. Functional IgHV1-69 gene rearrangements were detected in 32 cases (9.7%), 31 of which were characterised further. Seven (22.6%) were found to have undergone somatic hypermutation. This subgroup had shorter and more diverse complementarity determining region 3 (CDR3) sequences compared with unmutated IgHV1-69 cases. In addition, mutated IgHV1-69 gene status was associated with lower cell surface CD38 expression and less progressive disease as monitored by Binet staging, lymphocyte doubling time and requirement of chemotherapeutic intervention. To conclude, we present data confirming that IgHV1-69 gene rearrangements in CLL are not exclusively associated with unmutated IgHV status. In addition, we show that a somatically hypermutated subgroup may demonstrate more indolent characteristics despite the general association of IgHV1-69 gene usage with aggressive disease.
Authors:
Leeona Galligan; Mark A Catherwood; Christine Matthews; T C M 'Curly' Morris; H Dennis Alexander
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Leukemia & lymphoma     Volume:  49     ISSN:  1029-2403     ISO Abbreviation:  Leuk. Lymphoma     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-04-09     Completed Date:  2008-08-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9007422     Medline TA:  Leuk Lymphoma     Country:  England    
Other Details:
Languages:  eng     Pagination:  763-8     Citation Subset:  IM    
Affiliation:
Hemato-Oncology Laboratory, Department of Hematology, Belfast City Hospital, Belfast, United Kingdom. leeona.galligan@belfasttrust.hscni.net
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Antigens, CD38 / analysis
Complementarity Determining Regions / chemistry
Female
Gene Frequency
Gene Rearrangement
Humans
Immunoglobulin Heavy Chains / genetics*
Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis*,  genetics
Male
Mutation*
Prognosis
Chemical
Reg. No./Substance:
0/Complementarity Determining Regions; 0/Immunoglobulin Heavy Chains; EC 3.2.2.5/Antigens, CD38
Comments/Corrections
Comment In:
Leuk Lymphoma. 2008 Apr;49(4):648-9   [PMID:  18398727 ]

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