title: HLA-G expression in B chronic lymphocytic leukemia: a new prognostic marker?
abstract: Chronic lymphocytic leukemia (CLL) is characterized by a malignant clonal population of lymphocytes, which are usually of the B cell lineage. Classical Rai and Binet staging of CLL is being superseded by new prognostic markers. The mutational status of the immunoglobulin variable region heavy-chain genes segregates the disease into more benign and more malignant versions, and has been confirmed as an important prognostic marker in prospective clinical trials. A search for surrogate markers for this assay has led to flow cytometric assays for CD38 and ZAP-70 expression. The human leukocyte antigen G (HLA-G) molecule exhibits limited tissue distribution and a low polymorphism that generate seven HLA-G isoforms. HLA-G exerts multiple immunoregulatory functions. Recent studies indicate an ectopic up-regulation in tumor cells that may favor their escape from anti-tumor immune responses. For this report we studied HLA-G in parallel with CD38 and ZAP-70 in B-cell chronic lymphocytic leukemia (B-CLL) patients. HLA-G expression was studied retrospectively in circulating B-CLL cells from 20 patients by flow cytometry using the anti-HLA-G specific monoclonal antibody MEM/G9. The proportion of leukemic cells expressing HLA-G varied from 1 to 34%. We detected a statistically significant correlation between HLA-G positive (>12%) expression and progression free survival (p=0.045), but no correlation with CD38 and ZAP-70. We also detected a statistically significant difference between Binet stage A; B and C (p=0.046) and a positive correlation between IL-10 and HLA-G (p=0.044). We conclude that positive HLA-G has an effect on progression - free survival, when compared with CD38 and ZAP-70.
authors.affiliation: Department of Hematology, Gulhane Military Hospital, Istanbul/Ankara, Turkey. aleverikci@yahoo.com
authors.forename: Alev Akyol
authors.initials: AA
authors.lastname: Erikci
authors.forename: Bulent
authors.initials: B
authors.lastname: Karagoz
authors.forename: Mustafa
authors.initials: M
authors.lastname: Ozyurt
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ozturk
authors.forename: Selim
authors.initials: S
authors.lastname: Kilic
authors.forename: Oguz
authors.initials: O
authors.lastname: Bilgi
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D018450:Disease Progression; D018572:Disease-Free Survival; D005434:Flow Cytometry; D015870:Gene Expression; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies; D015854:Up-Regulation; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000096:biosynthesis / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D051997:ADP-ribosyl Cyclase 1