1). This broadly agreed with the detection of a 10-fold lower expression of DEK in mature cells from
peripheral blood compared to normal CD34 + cells as revealed in a previous study . However, not all terminally differentiated cells from different hematopoietic lineages exhibited similar expression of DEK, as higher DEK levels were observed in lymphoid cells as compared to mature myeloid cells. Within the myeloid lineage, monocytes had a 3-fold higher DEK expression than granulocytes (Fig. 1). Since DEK could be important in regulating granulocytic differentiation it may be expected that its expression this website could subsequently promote terminal differentiation in AML. In contrast, mice exhibited a markedly different expression pattern compared to that of humans (Fig. 1C & Supplementary Fig. 1). Most significantly, murine cells expressed elevated levels of Dek in GMPs and mature granulocytes as compared to the human myeloid cell equivalent (p < 0.001). However, DEK expression levels in monocytes were similar ( Fig. 1C). Overall, distinct DEK expression patterns
were observed during the progression of normal hematopoiesis, with DEK levels substantially reduced in mature cells compared Ku-0059436 cost to HSCs. Thus it appears that DEK levels during murine and human hematopoiesis highlight potential differences which may reflect cell type specific functions of DEK. However, the precise function of DEK in myeloid proliferation/differentiation remains unknown and requires further elucidation. Since DEK is generally found up-regulated in multiple human malignancies and is associated with the AML subgroup harboring the t(6:9) translocation it is possible that AML may also exhibit up-regulated DEK. However, four previous studies analyzing DEK expression in AML have given discordant results with over-expression in two studies and either no significant change or decreased expression in the others. Consequently this study aimed to clarify the expression status Selleck Rucaparib of DEK in AML. Analysis of DEK expression in three datasets of AML patients
indicated that DEK was not over-expressed and may actually be under-expressed in the majority of cases. Furthermore, dividing the AML patients into different subtypes detected no significant change or decreased DEK expression (Fig. 2). In agreement with our findings, a previous study of 14 APL cases, which possess the t(15;17) translocation and have a favorable prognosis, showed that there was no significant change in DEK expression. Analysis of over 500 pediatric AML samples from the Oncomine dataset , combined with over 600 adult samples in the MILE and LAML studies plus collated microarrays from the Hemaexplorer dataset, totaling more than 1000 cases of AML, supported an association of reduced DEK expression in AML.