| http://purl.uniprot.org/citations/28630052 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28630052 | http://www.w3.org/2000/01/rdf-schema#comment | "ETV6-RUNX1 is associated with the most common subtype of childhood leukemia. As few ETV6-RUNX1 carriers develop precursor B-cell acute lymphocytic leukemia (pB-ALL), the underlying genetic basis for development of full-blown leukemia remains to be identified, but the appearance of leukemia cases in time-space clusters keeps infection as a potential causal factor. Here, we present in vivo genetic evidence mechanistically connecting preleukemic ETV6-RUNX1 expression in hematopoetic stem cells/precursor cells (HSC/PC) and postnatal infections for human-like pB-ALL. In our model, ETV6-RUNX1 conferred a low risk of developing pB-ALL after exposure to common pathogens, corroborating the low incidence observed in humans. Murine preleukemic ETV6-RUNX1 pro/preB cells showed high Rag1/2 expression, known for human ETV6-RUNX1 pB-ALL. Murine and human ETV6-RUNX1 pB-ALL revealed recurrent genomic alterations, with a relevant proportion affecting genes of the lysine demethylase (KDM) family. KDM5C loss of function resulted in increased levels of H3K4me3, which coprecipitated with RAG2 in a human cell line model, laying the molecular basis for recombination activity. We conclude that alterations of KDM family members represent a disease-driving mechanism and an explanation for RAG off-target cleavage observed in humans. Our results explain the genetic basis for clonal evolution of an ETV6-RUNX1 preleukemic clone to pB-ALL after infection exposure and offer the possibility of novel therapeutic approaches. Cancer Res; 77(16); 4365-77. ©2017 AACR."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-17-0701"xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Chen C."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Bhatia S."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Fischer U."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Borkhardt A."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Sanchez-Garcia I."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Bartenhagen C."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Muschen M."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Gombert M."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "De Las Rivas J."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Dugas M."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Garcia-Sanchez A."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Cobaleda C."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Garcia-Criado F.J."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Gonzalez-Herrero I."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Vicente-Duenas C."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Hauer J."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Blanco O."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Schafer D."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Auer F."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Linka R.M."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Garcia-Cenador M.B."xsd:string |
| http://purl.uniprot.org/citations/28630052 | http://purl.uniprot.org/core/author | "Okpanyi V."xsd:string |