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Multi‐dimensional analysis identifies an immune signature predicting response to decitabine treatment in elderly patients with AML

Decitabine is a DNA‐hypomethylating agent that has been widely applied for the treatment of acute myeloid leukaemia (AML) patients who are elderly or unfit for intensive therapy. Although effective, the complete response rate to decitabine is only around 30% and the overall survival remains poor. Em...

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Autores principales: Zhao, Chenchen, Jia, Bei, Wang, Ming, Schell, Todd D., Claxton, David F., Ehmann, W Christopher, Rybka, Witold B., Mineishi, Shin, Naik, Seema, Songdej, Natthapol, Sivik, Jeff M., Hohl, Raymond J., Zeng, Hui, Zheng, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065206/
https://www.ncbi.nlm.nih.gov/pubmed/31573077
http://dx.doi.org/10.1111/bjh.16228
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author Zhao, Chenchen
Jia, Bei
Wang, Ming
Schell, Todd D.
Claxton, David F.
Ehmann, W Christopher
Rybka, Witold B.
Mineishi, Shin
Naik, Seema
Songdej, Natthapol
Sivik, Jeff M.
Hohl, Raymond J.
Zeng, Hui
Zheng, Hong
author_facet Zhao, Chenchen
Jia, Bei
Wang, Ming
Schell, Todd D.
Claxton, David F.
Ehmann, W Christopher
Rybka, Witold B.
Mineishi, Shin
Naik, Seema
Songdej, Natthapol
Sivik, Jeff M.
Hohl, Raymond J.
Zeng, Hui
Zheng, Hong
author_sort Zhao, Chenchen
collection PubMed
description Decitabine is a DNA‐hypomethylating agent that has been widely applied for the treatment of acute myeloid leukaemia (AML) patients who are elderly or unfit for intensive therapy. Although effective, the complete response rate to decitabine is only around 30% and the overall survival remains poor. Emerging data support that regulation of DNA methylation is critical to control immune cell development, differentiation and activation. We hypothesize that defining how decitabine influences the immune responses in AML will facilitate the development of novel immune‐based leukaemia therapeutics. Here, we performed phenotypic and functional immune analysis on clinical samples from AML patients receiving decitabine treatment and demonstrated a significant impact of decitabine on the immune system. T‐cell expression of inhibitory molecules was upregulated and the ability of CD8 T cells to produce cytokines was decreased upon decitabine treatment. Importantly, in an unbiased comprehensive analysis, we identified a unique immune signature containing a cluster of key immune markers that clearly separate patients who achieved complete remission after decitabine from those who failed to do so. Therefore, this immune signature has a strong predictive value for clinical response. Collectively, our study suggests that immune‐based analyses may predict clinical response to decitabine and provide a therapeutic strategy to improve the treatment of AML.
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spelling pubmed-70652062020-03-16 Multi‐dimensional analysis identifies an immune signature predicting response to decitabine treatment in elderly patients with AML Zhao, Chenchen Jia, Bei Wang, Ming Schell, Todd D. Claxton, David F. Ehmann, W Christopher Rybka, Witold B. Mineishi, Shin Naik, Seema Songdej, Natthapol Sivik, Jeff M. Hohl, Raymond J. Zeng, Hui Zheng, Hong Br J Haematol Haematological Malignancy – Clinical Decitabine is a DNA‐hypomethylating agent that has been widely applied for the treatment of acute myeloid leukaemia (AML) patients who are elderly or unfit for intensive therapy. Although effective, the complete response rate to decitabine is only around 30% and the overall survival remains poor. Emerging data support that regulation of DNA methylation is critical to control immune cell development, differentiation and activation. We hypothesize that defining how decitabine influences the immune responses in AML will facilitate the development of novel immune‐based leukaemia therapeutics. Here, we performed phenotypic and functional immune analysis on clinical samples from AML patients receiving decitabine treatment and demonstrated a significant impact of decitabine on the immune system. T‐cell expression of inhibitory molecules was upregulated and the ability of CD8 T cells to produce cytokines was decreased upon decitabine treatment. Importantly, in an unbiased comprehensive analysis, we identified a unique immune signature containing a cluster of key immune markers that clearly separate patients who achieved complete remission after decitabine from those who failed to do so. Therefore, this immune signature has a strong predictive value for clinical response. Collectively, our study suggests that immune‐based analyses may predict clinical response to decitabine and provide a therapeutic strategy to improve the treatment of AML. John Wiley and Sons Inc. 2019-10-01 2020-03 /pmc/articles/PMC7065206/ /pubmed/31573077 http://dx.doi.org/10.1111/bjh.16228 Text en © 2019 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Haematological Malignancy – Clinical
Zhao, Chenchen
Jia, Bei
Wang, Ming
Schell, Todd D.
Claxton, David F.
Ehmann, W Christopher
Rybka, Witold B.
Mineishi, Shin
Naik, Seema
Songdej, Natthapol
Sivik, Jeff M.
Hohl, Raymond J.
Zeng, Hui
Zheng, Hong
Multi‐dimensional analysis identifies an immune signature predicting response to decitabine treatment in elderly patients with AML
title Multi‐dimensional analysis identifies an immune signature predicting response to decitabine treatment in elderly patients with AML
title_full Multi‐dimensional analysis identifies an immune signature predicting response to decitabine treatment in elderly patients with AML
title_fullStr Multi‐dimensional analysis identifies an immune signature predicting response to decitabine treatment in elderly patients with AML
title_full_unstemmed Multi‐dimensional analysis identifies an immune signature predicting response to decitabine treatment in elderly patients with AML
title_short Multi‐dimensional analysis identifies an immune signature predicting response to decitabine treatment in elderly patients with AML
title_sort multi‐dimensional analysis identifies an immune signature predicting response to decitabine treatment in elderly patients with aml
topic Haematological Malignancy – Clinical
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065206/
https://www.ncbi.nlm.nih.gov/pubmed/31573077
http://dx.doi.org/10.1111/bjh.16228
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