title: The lymphocyte immunophenotypical pattern in chronic lymphocytic leukemia associated with hepatitis viral infections.
abstract: BACKGROUND
  Chronic lymphoproliferative disorders (CLD) are frequently found in patients with hepatitis viral infections, which can lead to changes in pathogenesis. Hepatitis viruses are hepatotrope viruses, potentially lymphotrope and also potentially oncogenic (hepatocellular carcinoma) viruses. HBV and HCV are involved in autoimmune disorders and in the ethiopathogeny of chronic lymphoproliferative disorders.
  
  
  OBJECTIVE
  Detection of immunophenotype changes of malignant lymphocytes in CLD--especially CLL--associated with hepatitis viral infections.
  
  
  METHODS
  Bone marrow aspirate, peripheral blood samples on EDTA were available for analysis from 58 patients from a follow-up schedule of the Department of Hematology SUUB from March 2008 until June 2009. The patients were diagnosed with chronic lymphoproliferative disorders associated with hepatitis virus B/C/D infections. A group of 28 consecutive unselected patients with CLL who met the diagnostic criteria of the National Cancer Institute-Working Group (NCI NCIWG), and associated hepatitis viral infection (v-CLL) were studied for the expression of several immunophenotypical markers, in comparison to CLL patients without viral infection (control group). Immunophenotyping analysis was performed on a FACS Calibur flowcytometer with a large panel according to EGIL/WHO recommendations. The diagnosis was completed after the histological and immunochemical analysis from tumoral lesions.
  
  
  RESULTS
  Demographics characteristics--male/female ratio 1/2, average age 64 years. Disease type: 90% B-CLD, 5% T-CLD, 5% Hodgkin's disease. The viral infections: 58.53% HCV, 34.41% HBV, 2.43% HBV+HDV, 2.43% HCV+HDV, 2.43% HBV+HCV+HDV. We found in CLL with viral coinfection (v-CLL) cases an elevated expression of B-cell markers--CD19 (Md95/92), CD20 (Md 90/39), CD79b (Md58/31), CD23 (Md67/37). Poor prognosis markers have a higher expression in v-CLL: CD38 (Md49/24), Bcl2 (Md 46/5), cyclin D19 (Md 11/0.5). No change in ZAP-70 expression was observed: Md 59.5/59.1.
  
  
  CONCLUSIONS
  Hepatitis viruses could be involved in the pathogenesis of CLD, but as a trigger for a more aggressive outcome. Higher expression of B-cell markers CD19, CD20 in CLL with viral infection suggests a change to atypical CLL, sustained by elevated expression of known poor prognosis markers bcl-2, cyclin D1 and CD38. Lack of ZAP-70 expression could be explained by a strong correlation with a basic unmutated IgVH status, not related to the viral infection. We found a higher frequency of HCV infection in patients with CLD and especially in CLL patients, which were analyzed extensively for immunophenotypical changes. In the present study, we demonstrated that this CD5+ B cell population with clonal expansion, defining CLL patients, has a different immunophenotype, probably related to the hepatitis viral infection.
authors.affiliation: Hematology Department, Universitary Emergency Hospital, Bucharest, Romania.
authors.forename: H
authors.initials: H
authors.lastname: Bumbea
authors.forename: A M
authors.initials: AM
authors.lastname: Vladareanu
authors.forename: A
authors.initials: A
authors.lastname: Vintilescu
authors.forename: S
authors.initials: S
authors.lastname: Radesi
authors.forename: C
authors.initials: C
authors.lastname: Ciufu
authors.forename: M
authors.initials: M
authors.lastname: Onisai
authors.forename: C
authors.initials: C
authors.lastname: Baluta
authors.forename: M
authors.initials: M
authors.lastname: Begu
authors.forename: C
authors.initials: C
authors.lastname: Dobrea
authors.forename: V
authors.initials: V
authors.lastname: Arama
authors.forename: A
authors.initials: A
authors.lastname: Streinu-Cercel
authors.forename: S
authors.initials: S
authors.lastname: Arama
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D014408:Biomarkers, Tumor / Q000276:immunology; D005260:Female; D006505:Hepatitis / Q000150:complications* / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D015994:Incidence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications* / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015995:Prevalence
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor