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Chronic lymphocytic leukemias utilizing the V(H)3-21 gene display highly restricted V(lambda)2-14 gene use and homologous CDR3s: implicating recognition of a common antigen epitope
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2003 (English)In: Blood, ISSN 0006-4971, Vol. 101, no 12, 4952-4957 p.Article in journal (Refereed) Published
Abstract [en]

The immunoglobulin variable heavy chain (IgV(H)) gene mutation status is an important prognostic factor in chronic lymphocytic leukemia (CLL), since cases with mutated V-H genes show significantly longer survival than unmutated cases. Recently, we reported a preferential use of the V(H)3-21 gene in mutated CLL and showed that mutated V(H)3-21 cases had an inferior overall survival compared with other mutated CLL. In order to further characterize this subset, we performed VH gene analysis in 265 CLL cases and identified 31 V(H)3-21 cases (11.7%), 21 cases had mutated and 10 cases unmutated VH genes. Regardless Of VH gene mutation status, a poor overall survival was found in the VH3-21 cases with a median survival of 83 months. These survival data confirm that V(H)3-21 cases do not fit into the general prognostic grouping of mutated and unmutated CLL. A large fraction Of V(H)3-21 cases also demonstrated unique features with shorter lengths of the third complementarity determining region (CDR3) and CDR3s with highly homologous amino acid sequences. Furthermore, the V(H)3-21 cases showed a striking dominance of X light chain expression, and analysis of the Iglambda gene rearrangements revealed highly restricted use of the Vlambda2-14/J(lambda)3 genes in the majority of cases. Taken together, our new findings strengthen the suggestion that V(H)3-21-using cases comprise a new CLL entity, irrespective Of VH gene mutation status, and implicate that a common antigen epitope, perhaps of pathogenic significance, is recognized by the highly homologous V(H)3-21/V(lambda)2-14 Ig molecules expressed in individual tumors. (Blood. 2003,101:4952-4957).

Place, publisher, year, edition, pages
2003. Vol. 101, no 12, 4952-4957 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-47784DOI: 10.1182/blood-2002-11-3485OAI: diva2:268680
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2009-10-31

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Juliusson, Gunnar
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HematologyFaculty of Health SciencesDepartment of HaematologyOncology Department of Haematology UHL
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