Evidence for the involvement of pim-2, a new common proviral insertion site, in progression of lymphomas.

Abstract

We have compared proviral integrations near (putative) proto‐oncogenes in Moloney murine leukemia virus‐induced primary and transplanted T cell lymphomas. We previously found proviruses integrated near c‐myc, pim‐1, and N‐myc in primary tumors (Selten et al., 1984; Van Lohuizen et al., 1989a; Van Lohuizen et al., 1989b). We have now identified an additional common proviral integration site, called pim‐2, that carries somatically acquired proviruses in the majority of transplanted tumors. In primary tumors integration near pim‐2 is usually undetectable or present in only a minor fraction of the tumor cells. This subpopulation selectively grows out upon transplantation. Insertion near pim‐2 is a relatively late event in tumorigenesis and is often preceded by proviral insertions in other common insertion sites, yielding tumor clones which carry proviruses in up to three different common insertion sites within the same cell (c‐myc, pim‐1 and pim‐2). The data suggest that pim‐2 plays an important role in tumor progression.

What retroviruses teach us about the involvement of c-Myc in leukemias and lymphomas

“…These data suggested that Pim2 is important for tumor progression. 176 Pim1 and Pim2 have been classified in the same group 139 and, in agreement with this, MuLV infection of Pim1/c-Myc bi-transgenic mice targeted Gfi1, not Pim2. 177 The large number of genes identified as Myc collaborators has resulted in attempts to classify these genes into complementation groups.…”

PIM Kinase Inhibitors Downregulate STAT3Tyr705 Phosphorylation

“…The pim-1 proto-oncogene was first identified as a locus frequently activated by proviral integration in Moloney murine leukemia virus-induced mouse T-cell lymphomas (1,2), and pim-2 was identified as a gene frequently activated in secondary transplants of virus-induced lymphomas. PIM-3 was identified as a PIM-1-and PIM-2-related kinase (3). The oncogenic nature of PIM-1 and PIM-2 was confirmed by the observation that transgenic mice overexpressing these kinases in the lymphoid system develop lymphomas.…”

Runx2: A novel oncogenic effector revealed by in vivo complementation and retroviral tagging

“…Tumour DNA was screened for rearrangements in known oncogenes using DNA probes as follows: N-Myc, 450 bp PCR fragment (Baxter et al, 1996); Pim1, 835 bp PCR fragment from clone pPim1 (Cupyers et al, 1984); Pim2, 2.05 kb cDNA fragment (van der Lugt et al, 1995); Tic1, 1.3 kb PCR fragment from clone pMB20 (Breuer et al, 1989); Pal1, 1.45 kb PCR fragment from clone p11A2 (van Lohuizen et al, 1991); Bmi1, 596 bp PCR fragment from cDNA 13.1 (van Lohuizen et al, 1991); G®1, 1.5 kb XbaI/BamHI cDNA fragment (Gilks et al, 1993); Dsi1, 4 kb BamHI/EcoRI fragment corresponding to the dsi-SR probe (Vijaya et al, 1987); Evi5, cDNA probe (Liao et al, 1995); Ahi1, 800 bp PstI/HindIII fragment from clone p2-1 (Poirier et al, 1988); Runx1, 158 bp PCR fragment derived from the exon 1 of the RUNX1c isoform (Miyoshi et al, 1995). c-Myc rearrangements were identi®ed using a human c-MYC exon 3 probe, (Stewart et al, 1993) which cross hybridises with the murine c-Myc gene due to the high degree of homology between the human and murine genes.…”