Extracellular DEK, in turn, gains novel functions, exhibiting chemo-attractant properties, resulting in the attraction of certain immune cells such as leukocytes of the immune system to the site of inflammation [15] and [16]. It has been shown recently by the addition of exogenous recombinant DEK that it can also mediate functions of hematopoietic stem cells (HSC) by suppressing proliferation of hematopoietic progenitor cells (HPC) and enhancing engraftment

of long term repopulating cells [17] and [18]. Interestingly, DEK added to cells is taken up in a bioactive MS-275 ic50 form, moved to the nucleus and re-engages in its bona fide chromatin functions, thus suggesting the existence of a paracrine-loop-like mechanism [19]. Furthermore, DEK works in concert with the transcription factor C/EBPα, whose function can be impaired in AML [20]. DEK also has a long-standing and well-established association with oncogenesis,

as it is consistently over-expressed in a number of prevalent and hard-to-treat neoplasms (e.g. retinoblastoma, glioblastoma, melanoma and prostate cancer) [21]. High DEK expression has been shown to directly promote cellular transformation through bypassing major barriers to early oncogenesis and tumor maintenance such as apoptosis and senescence, thus establishing DEK as a bona fide oncogene [22], [23], [24], [25] and [26]. Furthermore, I-BET-762 mw its expression correlates with metastases and notorious chemoresistance of melanoma and other cancers [22], [24] and [27]. Besides the expression of the DEK-NUP214 fusion gene, two previous studies have indicated that DEK itself is over-expressed in AML [28] and [29]. In one study, DEK expression profiling was analyzed at diagnosis of 15 primary AML patients with normal and complex karyotypes [28] and quantitative reverse transcription

-PCR (qRT-PCR) suggested that DEK was over-expressed independently of karyotype in nine of these cases (60%). Similarly, a qRT-PCR approach showed DEK over-expression in 98% of cases from a cohort of 41 AML patients. Higher levels of DEK were associated with Atezolizumab order CD34 negative bone marrow samples and independent of the t(6;9) chromosomal translocation [29]. Conversely, DEK expression has been found to be diminished in pediatric AML in comparison to normal bone marrow [26]. In addition, a study of 14 acute promyelocytic leukemia (APL) patients harboring the t(15:17) translocation revealed a non-significant four-fold down-regulation of DEK expression [30]. Overall there are conflicting data regarding the expression status of DEK in AML patients both with or without the t(6;9) translocation.