1. ¹Clinic of Hematology, University Hospital, University of Duisburg-Essen, Essen, Germany
2. ²Institute of Cell Biology, University Hospital, University of Duisburg-Essen, Essen, Germany
3. ³Institute of Molecular Biology, University Hospital, University of Duisburg-Essen, Essen, Germany
4. ⁴Department of Internal Medicine (Cancer Research), University Hospital, University of Duisburg-Essen, Essen, Germany

Correspondence: Dr J Dürig, Clinic of Hematology, University Hospital, University of Duisburg-Essen, Hufelandstr. 55, Essen 45122, Germany. E-mail: jan.duerig@uni-essen.de

Received 4 March 2006; Revised 8 June 2006; Accepted 30 June 2006; Published online 17 August 2006.

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.