Characterization of immunoglobulin heavy and light chain gene expression in chronic lymphocytic leukemia and related disorders.
The incidence of chronic lymphocytic leukemia is low in the Japanese population compared with populations in western countries, suggesting a role for genetic factors in the occurrence of this disease. We have previously shown that chronic lymphocytic leukemia in Japan rarely expresses the immunoglobulin heavy chain variable region (IGHV) 1-69 gene (1 out of 43 patients, 2.3%), which is a gene most commonly expressed in chronic lymphocytic leukemia cases from western countries. In the current study, we extended the previous study by examining immunoglobulin heavy chain and light chain gene expression in 80 Japanese patients with chronic lymphocytic leukemia and in 52 Japanese patients with other leukemic chronic lymphoproliferative disorders. IGHV1-69 gene expression was again quite low in our cohort, found in only two patients: one with chronic lymphocytic leukemia and the other with splenic marginal zone lymphoma. The IGHV4-34 gene was most frequently expressed in chronic lymphocytic leukemia (27.5%), whereas it was rarely found in leukemic chronic lymphoproliferative disorders (7.7%, P = 0.005). There was also a significant difference in the expression of IGLV3-21 between chronic lymphocytic leukemia and leukemic chronic lymphoproliferative disorders (29.4 vs 4.8%, P = 0.018). The IGLV3-21 gene in the majority of chronic lymphocytic leukemia cases was associated with homologous complementarity determining region 3 sequences. Recent studies identified subsets of cases expressing almost identical B-cell receptors. We found that two patients with chronic lymphocytic leukemia and the patient with splenic marginal zone lymphoma expressed IGHV4-39/IGKV1-39 and IGHV1-69/IGKV3-20, respectively, which belong to these subsets.
Nakahashi
Hirotaka
H
Department of Medicine and Clinical Science, Graduate School of Medicine, Gunma University, Gunma, Japan.
Tsukamoto
Norifumi
N
Hashimoto
Yoko
Y
Koiso
Hiromi
H
Yokohama
Akihiko
A
Saitoh
Takayuki
T
Uchiumi
Hideki
H
Handa
Hiroshi
H
Murakami
Hirokazu
H
Nojima
Yoshihisa
Y
Karasawa
Masamitsu
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018941:Antigens, CD19 / Q000276:immunology / Q000378:metabolism; D018956:CD5 Antigens / Q000276:immunology / Q000378:metabolism; D015331:Cohort Studies; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007564:Japan; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism
D018941:Antigens, CD19; C530104:CCND1 protein, human; D018956:CD5 Antigens; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D017455:Receptors, IgE; D019938:Cyclin D1