2018
DOI: 10.1158/2159-8290.cd-17-0902
|View full text |Cite
|
Sign up to set email alerts
|

BRD4 Profiling Identifies Critical Chronic Lymphocytic Leukemia Oncogenic Circuits and Reveals Sensitivity to PLX51107, a Novel Structurally Distinct BET Inhibitor

Abstract: Bromodomain and extra-terminal (BET) family proteins are key regulators of gene expression in cancer. Herein, we utilize BRD4 profiling to identify critical pathways involved in pathogenesis of chronic lymphocytic leukemia (CLL). BRD4 is overexpressed in CLL and is enriched proximal to genes upregulated or expressed in CLL with known functions in disease pathogenesis and progression. These genes, including key members of the B-cell receptor (BCR) signaling pathway, provide a rationale for this therapeutic appr… Show more

Help me understand this report
View preprint versions

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

5
139
0
1

Year Published

2018
2018
2023
2023

Publication Types

Select...
6
1
1

Relationship

0
8

Authors

Journals

citations
Cited by 113 publications
(151 citation statements)
references
References 97 publications
5
139
0
1
Order By: Relevance
“…Treatment with JQ1 led to dramatic inhibition of cell proliferation and proved efficacious in xenografted mice with disseminated CLL tumors. Recently, a structurally dissimilar BET inhibitor PLX51107 was reported to have similar effects in pre-clinical models of CLL, with transcriptional disruption of B cell receptor signaling genes in proximity to BRD4-bound super enhancers including PAX5 (Ozer et al, 2018). Thus, this class of pharmacologic agent may prove useful for CLL therapy, perhaps in combination with other agents targeting B cell signaling.…”
Section: Discussionmentioning
confidence: 99%
“…Treatment with JQ1 led to dramatic inhibition of cell proliferation and proved efficacious in xenografted mice with disseminated CLL tumors. Recently, a structurally dissimilar BET inhibitor PLX51107 was reported to have similar effects in pre-clinical models of CLL, with transcriptional disruption of B cell receptor signaling genes in proximity to BRD4-bound super enhancers including PAX5 (Ozer et al, 2018). Thus, this class of pharmacologic agent may prove useful for CLL therapy, perhaps in combination with other agents targeting B cell signaling.…”
Section: Discussionmentioning
confidence: 99%
“…The structure of PLX51107 is reported previously (Ozer et al, 2018 PLX51107 and PLX72853 were provided by Plexxikon, Inc.…”
Section: Inhibitors Growth Factors and Antibodiesmentioning
confidence: 99%
“…Indeed, we have previously reported JQ1 to be highly effective in inhibiting the growth of GNAQ/GNA11 mutant UM cells associated with downregulation of DNA damage response genes, Bcl-xL and Rad51 (Ambrosini et al, 2015). A next-generation BET inhibitor, PLX51107 (Ozer et al, 2018;Plexxikon, Inc., Berkeley, CA), that has a half-life of 2.8 h and a broader therapeutic index, is currently being tested in clinical trials for patients with advanced malignancies including UM (NCT02683395). A next-generation BET inhibitor, PLX51107 (Ozer et al, 2018;Plexxikon, Inc., Berkeley, CA), that has a half-life of 2.8 h and a broader therapeutic index, is currently being tested in clinical trials for patients with advanced malignancies including UM (NCT02683395).…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…PLX51107 differentially altered the growth of mouse Braf V600E melanoma tumors, effects that were associated with the influx of TAM. PLX3397, a colony-stimulating factor-1 re- (Ao et al, 2017;Ozer et al, 2018).…”
mentioning
confidence: 99%