Increased expression of the hPim-2 gene in human chronic lymphocytic leukemia and non-Hodgkin lymphoma

Pim-1 and Pim-2 are murine proto-oncogenes implicated in lymphomagenesis. The aim of this study was to investigate whether the human Pim-2 (hPim-2) expression is altered in chronic lymphocytic leukemia (B-CLL) and non-Hodgkin's lymphomas (NHL). We analyzed hPim-2 expression in 48 patients with NHL and CLL by quantitative in-situ hybridization, quantitative RT-PCR and FACS analysis. In-situ hybridization revealed a 5.5 +/- 2.2 times higher expression of hPim-2 in NHL over normal lymphocytes ( P<0.001). Similarly, with quantitative RT-PCR, expression in NHL was 1.5 to 2.6 times higher in involved splenic foci compared to nearby uninvolved regions (n = 3). hPim-2 mRNA was increased 3-folds in B-CLL over normal B-cells ( P<0.006). The increased hPim-2 levels correlated with lymphocyte doubling time (DT), in that mRNA levels were two times greater in patients with rapid DT (P<0.006). Moreover, a significant correlation was found between hPim-2 expression and the Binet staging system of CLL (P<0.022). The hPIM-2 protein expression was also upregulated in CLL, as assessed by FACS analysis. Therefore, this report provides direct evidence for a linkage of hPim-2 upregulation to NHL and CLL in man. This relationship between hPim-2 and NHL and CLL raises a number of novel mechanistic options for the genesis and/or progression of some types of human lymphomas.