The Spt-Ada-Gcn5-acetyltransferase complex interaction motif of E2a is essential for a subset of transcriptional and oncogenic properties of E2a-Pbx1.

The oncogene E2a-Pbx1 is formed by the t(1;19) translocation, which joins the N-terminal transactivation domain of E2a with the C-terminal homeodomain of PBX1. The goal of this work was to elucidate the mechanisms by which E2a-Pbx1 can lead to deregulated target gene expression. For reporter constructs it was shown that E2a-Pbx1 can activate transcription through homodimer elements (TGATTGAT) or through heterodimer elements with Hox proteins (e.g. TGATTAAT). We show a novel mechanism by which E2a-Pbx1 activates transcription of EF-9 using a promoter in intron 1 of the EF-9 gene, resulting in an aminoterminal truncated transcript. Our results indicate that the LDFS motif of E2a is essential for the transactivation of EF-9, but dispensable for transactivation of fibroblast growth factor 15. The E2a LDFS motif was also essential for proliferation of NIH3T3 fibroblasts but was dispensable for the E2a-Pbx1-induced differentiation arrest of myeloid progenitors.

The hospital cost of vertebral fractures in the EU: estimates using national datasets.

The purpose of this study was to estimate the hospital cost of vertebral fractures in the EU using national datasets to explore some of the methodologic limitations associated with such an approach. Hospital costs for vertebral fractures across the EU were compared with the hospital costs associated with hip fractures. Additionally, these costs were placed into the health care context by making comparisons with national health care expenditure. All EU Ministries of Health were contacted to identify national datasets to estimate the average length of stay, cost per diem and the number of patients discharged with vertebral fractures. Where national information was not available expert opinion and data from the relevant literature were used instead. Countries show a marked difference in the length of stay between men and women, with differences ranging from 0.32 days in Austria to 20.2 days in Spain. The average hospitalization rate was found to be 8% across the EU, with higher rates found for men than for women. Interestingly a positive correlation between health expenditure per capita and hospitalization rates was found. The total cost of vertebral fractures in the EU was estimated at euro 377 million per year. Across the EU the hospital cost of a vertebral fracture was on average 63% that of a hip fracture. National datasets allow us to estimate the cost of vertebral fractures in the EU but show limitations. In the absence of large scale prospective studies, national datasets need to be further refined to ensure more accurate estimations of the cost of vertebral fractures in the EU.