| http://purl.uniprot.org/citations/34103329 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/34103329 | http://www.w3.org/2000/01/rdf-schema#comment | "Lineage-ambiguous leukemias are high-risk malignancies of poorly understood genetic basis. Here, we describe a distinct subgroup of acute leukemia with expression of myeloid, T lymphoid, and stem cell markers driven by aberrant allele-specific deregulation of BCL11B, a master transcription factor responsible for thymic T-lineage commitment and specification. Mechanistically, this deregulation was driven by chromosomal rearrangements that juxtapose BCL11B to superenhancers active in hematopoietic progenitors, or focal amplifications that generate a superenhancer from a noncoding element distal to BCL11B. Chromatin conformation analyses demonstrated long-range interactions of rearranged enhancers with the expressed BCL11B allele and association of BCL11B with activated hematopoietic progenitor cell cis-regulatory elements, suggesting BCL11B is aberrantly co-opted into a gene regulatory network that drives transformation by maintaining a progenitor state. These data support a role for ectopic BCL11B expression in primitive hematopoietic cells mediated by enhancer hijacking as an oncogenic driver of human lineage-ambiguous leukemia. SIGNIFICANCE: Lineage-ambiguous leukemias pose significant diagnostic and therapeutic challenges due to a poorly understood molecular and cellular basis. We identify oncogenic deregulation of BCL11B driven by diverse structural alterations, including de novo superenhancer generation, as the driving feature of a subset of lineage-ambiguous leukemias that transcend current diagnostic boundaries.This article is highlighted in the In This Issue feature, p. 2659."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.org/dc/terms/identifier | "doi:10.1158/2159-8290.cd-21-0145"xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Chen X."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Cheng Z."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Gu Z."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Ma X."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Kimura S."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Ma J."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Wu G."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Zhang J."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Xu B."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Yin J."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Yang W."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Yang J.J."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Chang T.C."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Dickerson K."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Qu C."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Iacobucci I."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Ferrando A.A."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Mead P.E."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Valentine M.B."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Wang V."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Evans W.E."xsd:string |
| http://purl.uniprot.org/citations/34103329 | http://purl.uniprot.org/core/author | "Hunger S.P."xsd:string |