AML Ganetespib chemical structure often arises from chromosomal translocations resulting in specific leukemia-associated fusion proteins. These chimeric gene products exhibit distinctive functions that impede upon normal cellular proliferation and/or differentiation and are utilized to classify AML into specific sub-types and risk groups of favorable, intermediate and adverse. The rare translocation t(6;9), present in 1–5% of AML cases [2], results in the production of the DEK-NUP214 (formerly CAN) fusion, which is associated with a particularly poor prognosis and a median age of 44 years at diagnosis. The DEK oncogene was originally identified from

this leukemic translocation, where the 5′ portion of the DEK gene located on chromosome 6p23 was fused to the

3′ region of the NUP214 gene found on chromosome 9q34 resulting in the 165 kDa DEK-NUP214 fusion [3]. The leukemogenic potential of the DEK-NUP214 protein was undecided as it was unable to completely block differentiation of hematopoietic progenitors [4]. Subsequent data from Oancea et al. indicated DEK-NUP214 could promote leukemic transformation of a subset of long term repopulating hematopoietic stem cells [5], clearly pointing to an important selleck screening library contribution of DEK-NUP214 to leukemia. Data from two studies have revealed that the expression of DEK-NUP214 may increase the overall protein production by targeting translation [6], and may additionally accelerate proliferation through up-regulation of the mTOR pathway [7]. A recent international multicenter study has concluded that DEK-NUP214 represents a unique subtype of AML accompanied by increased risk of relapse, NADPH-cytochrome-c2 reductase higher FMS-like tyrosine kinase 3 internal tamdem dulpication (FLT3 ITD) mutation frequency and a defined gene signature [8]. However,

the precise molecular function of this fusion gene and its disease contribution remain mostly elusive. Human DEK, 43 kDa in size, is an abundant and primarily chromatin-associated nuclear factor [9]. DEK exhibits a wide variety of molecular functions (e.g. regulation of gene expression, RNA biology, DNA repair, apoptosis, senescence, and chromatin structure), suggesting that it is critically involved in a myriad of cellular processes that relate to proliferation, differentiation, senescence and the maintenance of cell stemness [10]. Currently, it is believed that these functions are predominantly transmitted by the architectural functions of DEK within cellular DNA and chromatin [10]. DEK has two distinct DNA-binding domains (SAP-box and C-terminal DNA binding domain), which can induce intra- and intermolecular contacts that lead to the alteration of DNA and chromatin topology [11], [12] and [13]. It is thought that changes to cellular DEK levels are most likely involved in regulating genomic stability and gene expression through concerted action of epigenetic mechanisms and chromatin architectural functions [10].