| http://purl.uniprot.org/citations/30080177 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30080177 | http://www.w3.org/2000/01/rdf-schema#comment | "Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) is a new pathological entity with poor outcomes in T cell ALL (T-ALL) that is characterized by a high incidence of loss-of-function mutations in polycomb repressive complex 2 (PRC2) genes. We generated a mouse model of ETP-ALL by deleting Ezh2, one of the PRC2 genes, in p53-null hematopoietic cells. The loss of Ezh2 in p53-null hematopoietic cells impeded the differentiation of ETPs and eventually induced ETP-ALL-like disease in mice, indicating that PRC2 functions as a bona fide tumor suppressor in ETPs. A large portion of PRC2 target genes acquired DNA hypermethylation of their promoters following reductions in H3K27me3 levels upon the loss of Ezh2, which included pivotal T cell differentiation-regulating genes. The reactivation of a set of regulators by a DNA-demethylating agent, but not the transduction of single regulator genes, effectively induced the differentiation of ETP-ALL cells. Thus, PRC2 protects key T cell developmental regulators from DNA hypermethylation in order to keep them primed for activation upon subsequent differentiation phases, while its insufficiency predisposes ETPs to leukemic transformation. These results revealed a previously unrecognized epigenetic switch in response to PRC2 dysfunction and provide the basis for specific rational epigenetic therapy for ETP-ALL with PRC2 insufficiency."xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci94645"xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/author | "Iwama A."xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/author | "Kanai A."xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/author | "Matsui H."xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/author | "Wang C."xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/author | "Sato D."xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/author | "Aoyama K."xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/author | "Kubota S."xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/author | "Koide S."xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/author | "Oshima M."xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/author | "Bai J."xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/author | "Nagao T."xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/author | "Sashida G."xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/author | "Nakajima-Takagi Y."xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/author | "Nakano-Yokomizo T."xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/author | "Matsubayashi J."xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/author | "Mochizuki-Kashio M."xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/name | "J Clin Invest"xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/pages | "3872-3886"xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/title | "Ezh2 loss propagates hypermethylation at T cell differentiation-regulating genes to promote leukemic transformation."xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://purl.uniprot.org/core/volume | "128"xsd:string |
| http://purl.uniprot.org/citations/30080177 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/30080177 |