> Detailanzeige

Montefiori, Lindsey E.; Bendig, Sonja; Gu, Zhaohui; Chen, Xiaolong; Pölönen, Petri; Ma, Xiaotu; Murison, Alex; Zeng, Andy; Garcia-Prat, Laura; Dickerson, Kirsten; Iacobucci, Ilaria; Abdelhamed, Sherif; Hiltenbrand, Ryan; Mead, Paul E.; Mehr, Cyrus M.; Xu, Beisi; Cheng, Zhongshan; Chang, Ti-Cheng; Westover, Tamara; Ma, Jing; Stengel, Anna; Kimura, Shunsuke; Qu, Chunxu; Valentine, Marcus B.; [...]

Enhancer Hijacking Drives Oncogenic BCL11B Expression in Lineage-Ambiguous Stem Cell Leukemia

Literatur-
verwaltung

Zur
Merkliste

Lösche von
Merkliste

Per Whatsapp teilen

Schließen

Merkliste



Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
  • Medientyp: E-Artikel
  • Titel: Enhancer Hijacking Drives Oncogenic BCL11B Expression in Lineage-Ambiguous Stem Cell Leukemia
  • Beteiligte: Montefiori, Lindsey E.; Bendig, Sonja; Gu, Zhaohui; Chen, Xiaolong; Pölönen, Petri; Ma, Xiaotu; Murison, Alex; Zeng, Andy; Garcia-Prat, Laura; Dickerson, Kirsten; Iacobucci, Ilaria; Abdelhamed, Sherif; Hiltenbrand, Ryan; Mead, Paul E.; Mehr, Cyrus M.; Xu, Beisi; Cheng, Zhongshan; Chang, Ti-Cheng; Westover, Tamara; Ma, Jing; Stengel, Anna; Kimura, Shunsuke; Qu, Chunxu; Valentine, Marcus B.; [...]
  • Erschienen: American Association for Cancer Research (AACR), 2021
  • Erschienen in: Cancer Discovery
  • Sprache: Englisch
  • DOI: 10.1158/2159-8290.cd-21-0145
  • ISSN: 2159-8274; 2159-8290
  • Schlagwörter: Oncology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title> <jats:sec> <jats:title /> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Significance:</jats:title> <jats:p>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.</jats:p> <jats:p>This article is highlighted in the In This Issue feature, p. 2659</jats:p> </jats:sec>
  • Zugangsstatus: Freier Zugang