D9, a novel 3-Deazaneplanocin A (DZNep) analog, is efficacious in targeting acute myeloid leukemia (AML) (Chemotherapy)

ABSTRACT: We and others have previously reported that 3-Deazaneplanocin A (DZNep) is a histone methylation inhibitor that has a wide range anticancer effects in a variety of human cancers. Here, using acute myeloid leukemia as a model, we reported a less toxic analog of DZNep, named D9, that is shown to be efficacious in both cell lines and patient samples of AML. Gene expression analysis in a panel of AML cell lines treated with D9 identified a set of genes that is associated with D9 sensitivity and is implicated in multiple oncogenic signaling pathways. Moreover, we show that D9 is able to deplete the leukemia stem cells (LSC) and abolish chemotherapy-induced LSC enrichment, leading to dramatic elimination of AML cell survival and associated gene expression when combined with chemotherapy. Thus, D9 appears to be a robust epigenetic compound that may constitute a potential for AML therapy. We found D9 treatment depleted chemotherapy-induced LSC. We next sought to characterize the molecular changes induce by the chemotherapy that is antagonized by D9. To do this, TF-1a cells before and after Ara-C or ADR treatment or co-treated with D9 were harvested for RNA isolation and genome-wide transcription profilling.

ORGANISM(S): Homo sapiens

SUBMITTER: Xia Jiang 

PROVIDER: E-GEOD-59625 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress