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Transcriptome-Based Co-Expression of BRD4 and PD-1/PD-L1 Predicts Poor Overall Survival in Patients With Acute Myeloid Leukemia

Positive response to PD-1/PD-L1 blockades was observed in the treatment of solid tumors. However, the clinical response to PD-1/PD-L1 blockade varied in patients with acute myeloid leukemia (AML). It is thought that there are factors other than PD-1 and PD-L1 that may affect the effect of immunother...

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Autores principales: Chen, Cunte, Xu, Ling, Gao, Rili, Wang, Shunqing, Zhang, Yuping, Wang, Caixia, Zeng, Chengwu, Li, Yangqiu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917577/
https://www.ncbi.nlm.nih.gov/pubmed/33658927
http://dx.doi.org/10.3389/fphar.2020.582955
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author Chen, Cunte
Xu, Ling
Gao, Rili
Wang, Shunqing
Zhang, Yuping
Wang, Caixia
Zeng, Chengwu
Li, Yangqiu
author_facet Chen, Cunte
Xu, Ling
Gao, Rili
Wang, Shunqing
Zhang, Yuping
Wang, Caixia
Zeng, Chengwu
Li, Yangqiu
author_sort Chen, Cunte
collection PubMed
description Positive response to PD-1/PD-L1 blockades was observed in the treatment of solid tumors. However, the clinical response to PD-1/PD-L1 blockade varied in patients with acute myeloid leukemia (AML). It is thought that there are factors other than PD-1 and PD-L1 that may affect the effect of immunotherapy. This study explored the impact of transcriptome-based co-expression of bromodomain containing 4 (BRD4) and PD-1/PD-L1 on the overall survival (OS) of patients with AML, in order to understand whether BRD4 would affect the effect of PD-1/PD-L1 blockades. Bone marrow samples from 59 AML patients in our clinical center and data of 176 patients from the Cancer Genome Atlas (TCGA) database were used for OS analysis and validation. It was found that increased expression of BRD4 was associated with poor OS in AML patients. Moreover, co-expression of BRD4 with PD-1 or PD-L1 was related to poor OS. The co-expression of BRD4 and PD-L1 was better than BRD4 and PD-1 for OS prediction. Furthermore, co-expression of BRD4 and PD-L1 was positively correlated with high tumor mutation burden, which contributed to poor OS in AML patients. Additionally, the co-expression of BRD4 and PD-L1 was associated with poor OS in non-acute promyelocytic leukemia patients with intermediate/high risk or under 60 years. Our results suggest that transcriptome-based co-expression of BRD4 and PD-L1 is a predictor for poor OS in AML patients, which might provide novel insight into designing combinational targeted therapy for AML.
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spelling pubmed-79175772021-03-02 Transcriptome-Based Co-Expression of BRD4 and PD-1/PD-L1 Predicts Poor Overall Survival in Patients With Acute Myeloid Leukemia Chen, Cunte Xu, Ling Gao, Rili Wang, Shunqing Zhang, Yuping Wang, Caixia Zeng, Chengwu Li, Yangqiu Front Pharmacol Pharmacology Positive response to PD-1/PD-L1 blockades was observed in the treatment of solid tumors. However, the clinical response to PD-1/PD-L1 blockade varied in patients with acute myeloid leukemia (AML). It is thought that there are factors other than PD-1 and PD-L1 that may affect the effect of immunotherapy. This study explored the impact of transcriptome-based co-expression of bromodomain containing 4 (BRD4) and PD-1/PD-L1 on the overall survival (OS) of patients with AML, in order to understand whether BRD4 would affect the effect of PD-1/PD-L1 blockades. Bone marrow samples from 59 AML patients in our clinical center and data of 176 patients from the Cancer Genome Atlas (TCGA) database were used for OS analysis and validation. It was found that increased expression of BRD4 was associated with poor OS in AML patients. Moreover, co-expression of BRD4 with PD-1 or PD-L1 was related to poor OS. The co-expression of BRD4 and PD-L1 was better than BRD4 and PD-1 for OS prediction. Furthermore, co-expression of BRD4 and PD-L1 was positively correlated with high tumor mutation burden, which contributed to poor OS in AML patients. Additionally, the co-expression of BRD4 and PD-L1 was associated with poor OS in non-acute promyelocytic leukemia patients with intermediate/high risk or under 60 years. Our results suggest that transcriptome-based co-expression of BRD4 and PD-L1 is a predictor for poor OS in AML patients, which might provide novel insight into designing combinational targeted therapy for AML. Frontiers Media S.A. 2021-02-01 /pmc/articles/PMC7917577/ /pubmed/33658927 http://dx.doi.org/10.3389/fphar.2020.582955 Text en Copyright © 2021 Chen, Xu, Gao, Wang, Zhang, Wang, Zeng and Li. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Chen, Cunte
Xu, Ling
Gao, Rili
Wang, Shunqing
Zhang, Yuping
Wang, Caixia
Zeng, Chengwu
Li, Yangqiu
Transcriptome-Based Co-Expression of BRD4 and PD-1/PD-L1 Predicts Poor Overall Survival in Patients With Acute Myeloid Leukemia
title Transcriptome-Based Co-Expression of BRD4 and PD-1/PD-L1 Predicts Poor Overall Survival in Patients With Acute Myeloid Leukemia
title_full Transcriptome-Based Co-Expression of BRD4 and PD-1/PD-L1 Predicts Poor Overall Survival in Patients With Acute Myeloid Leukemia
title_fullStr Transcriptome-Based Co-Expression of BRD4 and PD-1/PD-L1 Predicts Poor Overall Survival in Patients With Acute Myeloid Leukemia
title_full_unstemmed Transcriptome-Based Co-Expression of BRD4 and PD-1/PD-L1 Predicts Poor Overall Survival in Patients With Acute Myeloid Leukemia
title_short Transcriptome-Based Co-Expression of BRD4 and PD-1/PD-L1 Predicts Poor Overall Survival in Patients With Acute Myeloid Leukemia
title_sort transcriptome-based co-expression of brd4 and pd-1/pd-l1 predicts poor overall survival in patients with acute myeloid leukemia
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917577/
https://www.ncbi.nlm.nih.gov/pubmed/33658927
http://dx.doi.org/10.3389/fphar.2020.582955
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