ORCID Profile
0000-0002-6990-8186
Current Organisation
Friedreich's Ataxia Research Alliance
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Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540642.V1
Abstract: This file contains Supplementary Tables 1-15 detailing clinical and genomic information about each patient analyzed in this study, along with the results of RNA-seq and gene set enrichment analyses.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.C.6549439.V1
Abstract: Abstract 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 i BCL11B /i , a master transcription factor responsible for thymic T-lineage commitment and specification. Mechanistically, this deregulation was driven by chromosomal rearrangements that juxtapose i BCL11B /i to superenhancers active in hematopoietic progenitors, or focal lifications that generate a superenhancer from a noncoding element distal to i BCL11B /i . Chromatin conformation analyses demonstrated long-range interactions of rearranged enhancers with the expressed i BCL11B /i allele and association of i BCL11B /i with activated hematopoietic progenitor cell i cis /i -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 i BCL11B /i 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 i BCL11B /i driven by erse structural alterations, including i de novo /i superenhancer generation, as the driving feature of a subset of lineage-ambiguous leukemias that transcend current diagnostic boundaries. i This article is highlighted in the In This Issue feature, p. 2659 /i /
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540642
Abstract: This file contains Supplementary Tables 1-15 detailing clinical and genomic information about each patient analyzed in this study, along with the results of RNA-seq and gene set enrichment analyses.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540645.V1
Abstract: This file contains Supplementary Figures 1-23 with corresponding supplementary figure legends, as well as the legends for Supplementary Tables 1-15.
Publisher: American Association for Cancer Research (AACR)
Date: 08-06-2021
DOI: 10.1158/2159-8290.CD-21-0145
Abstract: 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 erse 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
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.C.6549439
Abstract: Abstract 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 i BCL11B /i , a master transcription factor responsible for thymic T-lineage commitment and specification. Mechanistically, this deregulation was driven by chromosomal rearrangements that juxtapose i BCL11B /i to superenhancers active in hematopoietic progenitors, or focal lifications that generate a superenhancer from a noncoding element distal to i BCL11B /i . Chromatin conformation analyses demonstrated long-range interactions of rearranged enhancers with the expressed i BCL11B /i allele and association of i BCL11B /i with activated hematopoietic progenitor cell i cis /i -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 i BCL11B /i 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 i BCL11B /i driven by erse structural alterations, including i de novo /i superenhancer generation, as the driving feature of a subset of lineage-ambiguous leukemias that transcend current diagnostic boundaries. i This article is highlighted in the In This Issue feature, p. 2659 /i /
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22540645
Abstract: This file contains Supplementary Figures 1-23 with corresponding supplementary figure legends, as well as the legends for Supplementary Tables 1-15.
Location: No location found
No related grants have been discovered for Marissa Rashkovan.