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.
Hematology Unit, Rabin Medical Center, Golda-Hasharon Campus, Petah-Tikva, and Sackler School of Medicine, Tel-Aviv University, Israel. amosc@clalit.org.il
Amos M
AM
Cohen
Borislava
B
Grinblat
Hanna
H
Bessler
Donald
D
Kristt
Alona
A
Kremer
Ariel
A
Schwartz
Marisa
M
Halperin
Sarah
S
Shalom
Drorit
D
Merkel
Jeremy
J
Don
D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
C490587:PIM2 protein, human; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D017346:Protein Serine-Threonine Kinases