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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADP-ribosyl Cyclase 1 / genetics*
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ADP-ribosyl Cyclase 1 / metabolism
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Aged
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Aged, 80 and over
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Angiopoietin-2 / genetics
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Angiopoietin-2 / metabolism
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B-Lymphocytes / pathology
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B-Lymphocytes / physiology
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Cell Differentiation
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Cohort Studies
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Female
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Flow Cytometry
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Gene Expression Regulation, Leukemic*
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Humans
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Leukemia, Lymphocytic, Chronic, B-Cell / classification
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Leukemia, Lymphocytic, Chronic, B-Cell / epidemiology
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Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
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Male
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Membrane Glycoproteins / genetics*
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Membrane Glycoproteins / metabolism
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Middle Aged
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Neovascularization, Pathologic / genetics
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Oligonucleotide Array Sequence Analysis
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Prognosis
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcr / metabolism
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism
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Risk Factors
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Signal Transduction / genetics
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ZAP-70 Protein-Tyrosine Kinase / genetics*
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ZAP-70 Protein-Tyrosine Kinase / metabolism
Substances
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Angiopoietin-2
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FCRL2 protein, human
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Membrane Glycoproteins
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PIM2 protein, human
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Proto-Oncogene Proteins
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Receptors, Cell Surface
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ZAP-70 Protein-Tyrosine Kinase
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BCR protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-bcr
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CD38 protein, human
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ADP-ribosyl Cyclase 1