2 & Supplementary Fig. 2). Importantly, this observed pattern of reduced DEK expression was also seen at the protein level using a distinctively different AML cohort that was analyzed by immunohistochemistry on newly created selleck screening library AML TMAs. Also, low levels of DEK expression were observed in most AML blasts, with only a few high DEK expression outliers, fully in agreement with the RNA expression data from the MILE, LAML and Hemaexplorer. Reduced DEK expression does not appear to be associated solely with pediatric leukemia as previously suggested, supported
by the inclusion of exclusively adult cases investigated throughout this study in all datasets and primary AML patient samples. Patients included represent a comprehensive range of AML subtypes and low DEK expression was found to be associated with all AML subtypes, which was verified in an independent cohort of primary samples (Fig. 2). Low DEK expression may be of prognostic relevance for the long term survival of AML patients but stratifying patients on the basis
of DEK expression levels indicated that there was no influence on patient survival either in the presence of absence of the favorable risk group of AML patients (Fig. 5 & Supplementary Fig. 3). The http://www.selleckchem.com/products/azd5363.html favorable group contains patients with APL, who have a good prognosis as ATRA treatment alleviates the block in differentiation. It is unknown whether DEK contributes to improved survival in the favorable risk group although in the study of APL patients Savli et al. [30], similarly to our study, found that DEK expression was reduced by a factor of 4 but this was not statistically significant. However, there Liothyronine Sodium is insufficient evidence to establish if DEK levels may have an effect on overall survival of the favorable risk group patients, especially those classified as promyelocytic. Based on the gene expression levels of DEK expression it can be concluded that DEK does not correlate with the survival of AML patients. In this study we investigated the expression of the DEK oncogene in three independent AML datasets and, contrary to current perception, established that DEK
is under-expressed compared to the equivalent normal myeloid cell. However, DEK did not influence overall survival of AML patients. DEK levels in normal hematopoietic differentiation of human and mouse revealed that DEK levels were associated with HPC and specific cell stages, hence suggesting distinct functions during myeloid differentiation for DEK. Although the precise function of DEK in myeloid proliferation and differentiation remains unknown, DEK may be playing an important role in hematopoiesis. However, it remains to be established whether DEK is important for leukemagenesis, except when involved in the t(6;9) translocation. The following are the supplementary data related to this article. Supplementary Fig. 1. Differential Dek expression during murine hematopoiesis. A.