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Lower BCL11B expression is associated with adverse clinical outcome for patients with myelodysplastic syndrome

Myelodysplastic syndrome (MDS) is an aggressive and genetically heterogeneous disease with poor prognosis. Cellular immune disorder is a common characteristic of this disease and is thought to be related to clinical outcome. Alterations in T cell clonal expansion and T cell dysfunction has been dete...

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Autores principales: Huang, Xin, Chen, Cunte, Zhong, Mengjun, Geng, Suxia, Zhao, Yujie, Li, Minming, Deng, Chenxin, Zeng, Lingji, Wu, Ping, Lu, Zesheng, Weng, Jianyu, Du, Xin, Li, Yangqiu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193904/
https://www.ncbi.nlm.nih.gov/pubmed/34112264
http://dx.doi.org/10.1186/s40364-021-00302-y
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author Huang, Xin
Chen, Cunte
Zhong, Mengjun
Geng, Suxia
Zhao, Yujie
Li, Minming
Deng, Chenxin
Zeng, Lingji
Wu, Ping
Lu, Zesheng
Weng, Jianyu
Du, Xin
Li, Yangqiu
author_facet Huang, Xin
Chen, Cunte
Zhong, Mengjun
Geng, Suxia
Zhao, Yujie
Li, Minming
Deng, Chenxin
Zeng, Lingji
Wu, Ping
Lu, Zesheng
Weng, Jianyu
Du, Xin
Li, Yangqiu
author_sort Huang, Xin
collection PubMed
description Myelodysplastic syndrome (MDS) is an aggressive and genetically heterogeneous disease with poor prognosis. Cellular immune disorder is a common characteristic of this disease and is thought to be related to clinical outcome. Alterations in T cell clonal expansion and T cell dysfunction has been detected in MDS patients. Little is known about whether there are immune biomarkers to evaluate the T cell alterations with clinical outcome. Previous studies have demonstrated that B-cell leukemia/lymphoma 11B (BCL11B) plays an important role in regulating T cell development and proliferation. In this study, the prognostic value of BCL11B for MDS patients was explored by analyzing RNA-seq data from 270 patients in two datasets in the Gene Expression Omnibus (GEO) database and real-time quantitative PCR data (qRT-PCR) of 31 bone marrow (BM) samples of MDS and 6 BM samples of patients with MDS progress to secondary acute myeloid leukemia (sAML) from our clinical center. The results demonstrated that BCL11B is significantly down-regulated in MDS patients as compared with healthy individuals (HIs). Importantly, lower BCL11B expression was found in MDS patients who were of high/very high risk, older than 60 y, or male and patients with sAML. Furthermore, low BCL11B expression appeared to be associated with poor overall survival (OS) for MDS patients, though the data were not yet significant enough at this point. In addition, BCL11B low-expressing MDS patients had shorter restricted mean survival time (RMST) than those with high BCL11B expression. Interestingly, BCL11B positively correlated with naive and activated memory CD4 + T cells, CD8 + T cells, and the T cell receptor complex genes CD3E and CD3G, but it negatively correlated with regulatory T cells (Treg). Additionally, co-occurrence of low BCL11B expression and CD3E and CD3G was associated with poor OS and shorter RMST. In conclusion, lower BCL11B expression in BM samples of MDS patients was associated with adverse clinical outcome. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40364-021-00302-y.
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spelling pubmed-81939042021-06-15 Lower BCL11B expression is associated with adverse clinical outcome for patients with myelodysplastic syndrome Huang, Xin Chen, Cunte Zhong, Mengjun Geng, Suxia Zhao, Yujie Li, Minming Deng, Chenxin Zeng, Lingji Wu, Ping Lu, Zesheng Weng, Jianyu Du, Xin Li, Yangqiu Biomark Res Letter to the Editor Myelodysplastic syndrome (MDS) is an aggressive and genetically heterogeneous disease with poor prognosis. Cellular immune disorder is a common characteristic of this disease and is thought to be related to clinical outcome. Alterations in T cell clonal expansion and T cell dysfunction has been detected in MDS patients. Little is known about whether there are immune biomarkers to evaluate the T cell alterations with clinical outcome. Previous studies have demonstrated that B-cell leukemia/lymphoma 11B (BCL11B) plays an important role in regulating T cell development and proliferation. In this study, the prognostic value of BCL11B for MDS patients was explored by analyzing RNA-seq data from 270 patients in two datasets in the Gene Expression Omnibus (GEO) database and real-time quantitative PCR data (qRT-PCR) of 31 bone marrow (BM) samples of MDS and 6 BM samples of patients with MDS progress to secondary acute myeloid leukemia (sAML) from our clinical center. The results demonstrated that BCL11B is significantly down-regulated in MDS patients as compared with healthy individuals (HIs). Importantly, lower BCL11B expression was found in MDS patients who were of high/very high risk, older than 60 y, or male and patients with sAML. Furthermore, low BCL11B expression appeared to be associated with poor overall survival (OS) for MDS patients, though the data were not yet significant enough at this point. In addition, BCL11B low-expressing MDS patients had shorter restricted mean survival time (RMST) than those with high BCL11B expression. Interestingly, BCL11B positively correlated with naive and activated memory CD4 + T cells, CD8 + T cells, and the T cell receptor complex genes CD3E and CD3G, but it negatively correlated with regulatory T cells (Treg). Additionally, co-occurrence of low BCL11B expression and CD3E and CD3G was associated with poor OS and shorter RMST. In conclusion, lower BCL11B expression in BM samples of MDS patients was associated with adverse clinical outcome. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40364-021-00302-y. BioMed Central 2021-06-10 /pmc/articles/PMC8193904/ /pubmed/34112264 http://dx.doi.org/10.1186/s40364-021-00302-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Letter to the Editor
Huang, Xin
Chen, Cunte
Zhong, Mengjun
Geng, Suxia
Zhao, Yujie
Li, Minming
Deng, Chenxin
Zeng, Lingji
Wu, Ping
Lu, Zesheng
Weng, Jianyu
Du, Xin
Li, Yangqiu
Lower BCL11B expression is associated with adverse clinical outcome for patients with myelodysplastic syndrome
title Lower BCL11B expression is associated with adverse clinical outcome for patients with myelodysplastic syndrome
title_full Lower BCL11B expression is associated with adverse clinical outcome for patients with myelodysplastic syndrome
title_fullStr Lower BCL11B expression is associated with adverse clinical outcome for patients with myelodysplastic syndrome
title_full_unstemmed Lower BCL11B expression is associated with adverse clinical outcome for patients with myelodysplastic syndrome
title_short Lower BCL11B expression is associated with adverse clinical outcome for patients with myelodysplastic syndrome
title_sort lower bcl11b expression is associated with adverse clinical outcome for patients with myelodysplastic syndrome
topic Letter to the Editor
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193904/
https://www.ncbi.nlm.nih.gov/pubmed/34112264
http://dx.doi.org/10.1186/s40364-021-00302-y
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