bcl-2 and immunoglobulin gene rearrangement in patients with hepatitis C virus infection.
An association between chronic hepatitis C virus (HCV) infection and clonal proliferation of B cells, including B cell lymphoma, has recently been demonstrated. However, the mechanism of malignant transformation is still unknown. It has been shown that B cells from patients with type II mixed cryoglobulinaemia (MC), strongly express the antiapoptotic bcl-2 oncogene product. Therefore, we investigated a possible mechanism of lymphomagenesis, the occurrence of bcl-2 and immunoglobulin gene rearrangement (IgH) in HCV-infected patients. Three groups of patients were studied: (1) 44 patients with HCV and MC (anti-HCV and HCV RNA positive); (2) 59 patients with chronic HCV infection without MC; (3) 50 patients with chronic liver disease (CLD) not related to HCV infection. The t(14;18) translocation (MBR bcl-2-JH) and IgH rearrangement (FR3/JH) were detected by polymerase chain reaction (PCR) in peripheral mononuclear cells. bcl-2 translocation was detected in 17/44 (39%), 7/59 (12%) and in none of the patients of groups 1, 2 and 3 respectively (P < 0.01). Monoclonal IgH rearrangement was detected in 15/44 (34%), 5/59 (8.5%) and 2/50 (4%) patients of groups 1, 2 and 3 respectively (P < 0.05). HCV-infected patients had a higher prevalence of monoclonal IgH rearrangement and bcl-2 translocation than patients with CLD of other aetiologies. These data suggest that HCV may play a role in the multistep mechanism of lymphomagenesis by inducing clonal proliferation of B cells and inhibition of apoptosis.
Zuckerman
E
E
Liver Unit and the Department of Internal Medicine A, Bnai Zion Medical Centre, Haifa, Israel. elizuck@hotmail.com
Zuckerman
T
T
Sahar
D
D
Streichman
S
S
Attias
D
D
Sabo
E
E
Yeshurun
D
D
Rowe
J
J
D000328:Adult; D000368:Aged; D016009:Chi-Square Distribution; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D003449:Cryoglobulinemia / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D019254:Genes, bcl-2; D019698:Hepatitis C, Chronic / Q000235:genetics*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008223:Lymphoma / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D014178:Translocation, Genetic
D007143:Immunoglobulin Heavy Chains