Gene expression signatures separate B-cell chronic lymphocytic leukaemia prognostic subgroups defined by ZAP-70 and CD38 expression status

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.