Replication status as a marker for predisposition for lymphoma in patientswith chronic hepatitis C with and without cryoglobulinemia

Objective. Essential mixed cryoglobulinemia (EMC) type ii is associated wit h hepatitis C virus (HCV) in 90% of the patients with this disorder. A sign ificant subset of these patients is at risk to develop non-Hodgkin lymphoma (NHL). The objective of this study was to examine whether the presence of EMC, a presumably premalignant step of lymphoproliferation, is associated w ith changes in the replication state of normal structural genes. Materials and Methods. The study group included three subgroups: (1) seven patients with HCV without EMC; (2) eight patients with HCV associated with EMC. 3. Seven patients with follicular lymphoma; and (3) six healthy indivi duals served as control group. Monocolor fluorescent in situ hybridization (FISH) with probes to p53, RE-I, and 21q22 was applied to leukocytes nuclei for the evaluation of replication timing. Results. Asynchronous replication (SD) rate was similar in patients with NH L and those with HCV associated with EMC and both are significantly higher when compared to patients with HCV without EMC and to normal controls (p < 0.01) for each comparison. This held true for all studied loci (21q22, RB-1 , and p53). Patients infected by HCV (but without EMC) had a significantly higher rate of asynchronous pattern in comparison with healthy controls (p < 0.01). Conclusions. Patients with a "premalignant" clinical condition HCV with EMC already demonstrate asynchronous type of replication which is similar to p atients who already have an established malignant disease (i.e., NHL), In t he future, replication may be used to assess the risk of malignant transfor mation in patients with "benign" proliferation. (C) 2000 International Soci ety for Experimental Hematology. Published by Elsevier Science Inc.