Features of the overexpressed V1-69 genes in the unmutated subset of chronic lymphocytic leukemia are distinct from those in the healthy elderly repertoire
KN Potter, J Orchard, E Critchley… - Blood, The Journal …, 2003 - ashpublications.org
KN Potter, J Orchard, E Critchley, CI Mockridge, A Jose, FK Stevenson
Blood, The Journal of the American Society of Hematology, 2003•ashpublications.orgChronic lymphocytic leukemia (CLL) comprises 2 subsets, distinguished by expression of
unmutated or mutated VHgenes, with the former having a worse prognosis. Biased usage of
the V1-69 gene is found in unmutated cases and is combined with selected D gene
segments and JH6. It is controversial whether this is a CLL-associated feature or mirrors the
normal B-cell pattern. Since CLL is a disease of the elderly, where changes in the B-cell
repertoire may occur, we have analyzed V1-69 usage in the elderly (older than 75 years) …
unmutated or mutated VHgenes, with the former having a worse prognosis. Biased usage of
the V1-69 gene is found in unmutated cases and is combined with selected D gene
segments and JH6. It is controversial whether this is a CLL-associated feature or mirrors the
normal B-cell pattern. Since CLL is a disease of the elderly, where changes in the B-cell
repertoire may occur, we have analyzed V1-69 usage in the elderly (older than 75 years) …
Abstract
Chronic lymphocytic leukemia (CLL) comprises 2 subsets, distinguished by expression of unmutated or mutated VHgenes, with the former having a worse prognosis. Biased usage of the V1-69 gene is found in unmutated cases and is combined with selected D gene segments and JH6. It is controversial whether this is a CLL-associated feature or mirrors the normal B-cell pattern. Since CLL is a disease of the elderly, where changes in the B-cell repertoire may occur, we have analyzedV1-69 usage in the elderly (older than 75 years) population. Using monoclonal antibody (MoAb) G6, specific for 51p1-related V1-69 alleles, we found no increased expression with age. In 51p1-encoded immunoglobulin M (IgM), complementarity-determining region 3 (CDR3) length and frequency of D and JH genes were similar to those in the healthy young and distinct from those in CLL. These findings support the concept that CLL arises from B cells driven by antigen/superantigen and is not a stochastic event in the elderly B-cell population.
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