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

The Runx2 (Cbfa1, Pebp2 alphaA, Aml3) gene was previously identified as a f requent target for transcriptional activation by proviral insertion in T-ce ll lymphomas of CD2-MYC transgenic mice. We have recently shown that over-e xpression of the full-length, most highly expressed Runx2 isoform in the th ymus perturbs T-cell development, leads to development of spontaneous lymph omas at low frequency and is strongly synergistic with MSc. To gain further insight into the relationship of Runx2 to other lymphomagenic pathways, me tested the effect of combining the CD2-Runx2 transgene either with a Pim1 transgene (E mu -Pim1) or with the p53 null genotype, as each of these disp lays independent synergy with Myc, In both cases we observed synergistic tu mour development. However, Runx2 appeared to have a dominant effect on the tumour phenotype in each case, with most tumours conforming to the CD3(+), CD8(+), CD4(+/-) phenotype seen in CD2-Runx2 mice, Neonatal infection of CD 2-Runx2 mice with Moloney murine leukaemia virus (Moloney MLV) also led to a dramatic acceleration of tumour onset. Analysis of known Moloney MLV targ et genes in these lymphomas showed a high frequency of rearrangement at c-M yc or N-Myc (82%), and a significant number at Pim1 or Pim2 (23%), and at P al1/Gfi1 (18%), These results indicate that Runx2 makes a distinct contribu tion to T-cell lymphoma development which does not coincide with any of the oncogene complementation groups previously identified by retroviral taggin g.