| http://purl.uniprot.org/citations/26387755 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26387755 | http://www.w3.org/2000/01/rdf-schema#comment | "Acute myeloid leukemia (AML) is driven and sustained by leukemia stem cells (LSCs) with unlimited self-renewal capacity and resistance to chemotherapy. Mutation in the TP53 tumor suppressor is relatively rare in de novo AML; however, p53 can be regulated through post-translational mechanisms. Here, we show that p53 activity is inhibited in inv(16)(+) AML LSCs via interactions with the CBFβ-SMMHC (CM) fusion protein and histone deacetylase 8 (HDAC8). HDAC8 aberrantly deacetylates p53 and promotes LSC transformation and maintenance. HDAC8 deficiency or inhibition using HDAC8-selective inhibitors (HDAC8i) effectively restores p53 acetylation and activity. Importantly, HDAC8 inhibition induces apoptosis in inv(16)(+) AML CD34(+) cells, while sparing the normal hematopoietic stem cells. Furthermore, in vivo HDAC8i administration profoundly diminishes AML propagation and abrogates leukemia-initiating capacity of both murine and patient-derived LSCs. This study elucidates an HDAC8-mediated p53-inactivating mechanism promoting LSC activity and highlights HDAC8 inhibition as a promising approach to selectively target inv(16)(+) LSCs."xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.stem.2015.08.004"xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/author | "Cai Q."xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/author | "Liu H."xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/author | "Li L."xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/author | "Singh S."xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/author | "Qi J."xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/author | "Ho Y."xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/author | "Lin A."xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/author | "Kuo Y.H."xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/author | "McDonald T."xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/author | "Hua W.K."xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/author | "Huang W.J."xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/author | "Marcucci G."xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/author | "Chang C.I."xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/author | "Bhatia R."xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/author | "Chao S.W."xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/name | "Cell Stem Cell"xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/pages | "597-610"xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/title | "HDAC8 Inhibition Specifically Targets Inv(16) Acute Myeloid Leukemic Stem Cells by Restoring p53 Acetylation."xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://purl.uniprot.org/core/volume | "17"xsd:string |
| http://purl.uniprot.org/citations/26387755 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26387755 |
| http://purl.uniprot.org/citations/26387755 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/26387755 |