Somatically mutated Ig V(H)3-21 genes characterize a new subset of chronic lymphocytic leukemia.
Recent studies on the immunoglobulin variable heavy chain (IgV(H)) genes have revealed that B-cell chronic lymphocytic leukemia (B-CLL) consists of at least 2 clinical entities with either somatically mutated or unmutated V(H) genes. We have analyzed the V(H) gene mutation status and V(H) gene usage in 119 B-CLL cases and correlated them to overall survival. A novel finding was the preferential use of the V(H)3-21 gene in mutated cases, whereas biased V(H)1-69 gene usage was found in unmutated cases as previously reported. Interestingly, the subset of mutated cases using the V(H)3-21 gene displayed distinctive genotypic/phenotypic characteristics with shorter average length of the complementarity determining region 3 and clonal expression of lambda light chains. In addition, this mutated subset showed significantly shorter survival than other mutated cases and a similar clinical course to unmutated cases. We therefore suggest that B-CLL cases with mutated V(H)3-21 genes may constitute an additional entity of B-CLL.
Tobin
Gerard
G
Department of Genetics and Pathology, Uppsala University, SE-751 85 Uppsala, Sweden.
Thunberg
Ulf
U
Johnson
Anna
A
Thörn
Ingrid
I
Söderberg
Ola
O
Hultdin
Magnus
M
Botling
Johan
J
Enblad
Gunilla
G
Sällström
Jan
J
Sundström
Christer
C
Roos
Göran
G
Rosenquist
Richard
R
D000368:Aged; D022801:Complementarity Determining Regions / Q000235:genetics; D005260:Female; D005803:Genes, Immunoglobulin / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007146:Immunoglobulin lambda-Chains; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000145:classification* / Q000235:genetics* / Q000276:immunology; D008297:Male; D009154:Mutation; D010641:Phenotype; D015996:Survival Rate
D022801:Complementarity Determining Regions; D007146:Immunoglobulin lambda-Chains