title: Gene expression signatures separate B-cell chronic lymphocytic leukaemia prognostic subgroups defined by ZAP-70 and CD38 expression status.
abstract: B-cell chronic lymphocytic leukaemia (B-CLL) is a heterogenous disease with a highly variable clinical course and analysis of zeta-associated protein 70 (ZAP-70) and CD38 expression on B-CLL cells allowed for identification of patients with good (ZAP-70-CD38-) and poor (ZAP-70+CD38+) prognosis. DNA microarray technology was employed to compare eight ZAP-70+CD38+ with eight ZAP-70-CD38- B-CLL cases. The expression of 358 genes differed significantly between the two subgroups, including genes involved in B-cell receptor signaling, angiogenesis and lymphomagenesis. Three of these genes, that is, immune receptor translocation-associated protein 4 (IRTA4)/Fc receptor homologue 2 (FcRH2), angiopoietin 2 (ANGPT2) and Pim2 were selected for further validating studies in a cohort of 94 B-CLL patients. IRTA4/FcRH2 expression as detected by flow cytometry was significantly lower in the poor prognosis subgroup as compared to ZAP-70-CD38- B-CLL cells. In healthy individuals, IRTA4/FcRH2 protein expression was associated with a CD19+CD27+ memory cell phenotype. ANGPT2 plasma concentrations were twofold higher in the poor prognosis subgroup (P<0.05). Pim2 was significantly overexpressed in poor prognosis cases and Binet stage C. Disease progression may be related to proangiogenic processes and strong Pim2 expression.
authors.affiliation: Clinic of Hematology, University Hospital, University of Duisburg-Essen, Essen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hüttmann
authors.forename: L
authors.initials: L
authors.lastname: Klein-Hitpass
authors.forename: J
authors.initials: J
authors.lastname: Thomale
authors.forename: R
authors.initials: R
authors.lastname: Deenen
authors.forename: A
authors.initials: A
authors.lastname: Carpinteiro
authors.forename: H
authors.initials: H
authors.lastname: Nückel
authors.forename: P
authors.initials: P
authors.lastname: Ebeling
authors.forename: A
authors.initials: A
authors.lastname: Führer
authors.forename: J
authors.initials: J
authors.lastname: Edelmann
authors.forename: L
authors.initials: L
authors.lastname: Sellmann
authors.forename: U
authors.initials: U
authors.lastname: Dührsen
authors.forename: J
authors.initials: J
authors.lastname: Dürig
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D042702:Angiopoietin-2 / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000473:pathology / Q000502:physiology; D002454:Cell Differentiation; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000145:classification / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051562:Proto-Oncogene Proteins c-bcr / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics* / Q000378:metabolism
chemical_list: D042702:Angiopoietin-2; C422179:FCRL2 protein, human; D008562:Membrane Glycoproteins; C490587:PIM2 protein, human; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D051746:ZAP-70 Protein-Tyrosine Kinase; C496613:BCR protein, human; D017346:Protein Serine-Threonine Kinases; D051562:Proto-Oncogene Proteins c-bcr; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1