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Identification and validation of prognosis‐related DLX5 methylation as an epigenetic driver in myeloid neoplasms
The deregulated DLX gene family members DLX1/2/3/4/5/6 (DLXs) caused by DNA methylation has been demonstrated in various cancers with therapeutic target value. However, the potential role of DLXs methylation in myeloid neoplasms such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403826/ https://www.ncbi.nlm.nih.gov/pubmed/32508046 http://dx.doi.org/10.1002/ctm2.29 |
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author | Zhang, Ting‐juan Xu, Zi‐jun Gu, Yu Wen, Xiang‐mei Ma, Ji‐chun Zhang, Wei Deng, Zhao‐qun Leng, Jia‐yan Qian, Jun Lin, Jiang Zhou, Jing‐dong |
author_facet | Zhang, Ting‐juan Xu, Zi‐jun Gu, Yu Wen, Xiang‐mei Ma, Ji‐chun Zhang, Wei Deng, Zhao‐qun Leng, Jia‐yan Qian, Jun Lin, Jiang Zhou, Jing‐dong |
author_sort | Zhang, Ting‐juan |
collection | PubMed |
description | The deregulated DLX gene family members DLX1/2/3/4/5/6 (DLXs) caused by DNA methylation has been demonstrated in various cancers with therapeutic target value. However, the potential role of DLXs methylation in myeloid neoplasms such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) remains to be elucidated. Clinical significance of DLXs methylation/expression was analyzed in patient with AML and MDS. The functional roles of DLXs were determined in vitro. In the identification stage, we found that lower DLX5 expression was correlated with prognosis in AML among all DLXs analyzed by The Cancer Genome Atlas datasets. In the validation stage, we revealed that reduced DLX5 expression was frequently occurred, and was also correlated with promoter hypermethylation in AML evaluated by targeted bisulfite sequencing. Epigenetic studies also showed that DLX5 promoter DNA methylation was associated with its expression. By quantitative polymerase chain reaction, we also validated that DLX5 hypermethylation was frequent event in both AML and MDS, and also correlated with MDS transformation to leukemia. Moreover, DLX5 hypermethylation was associated with lower rate of complete remission and shorter time of leukemia‐free/overall survival, and was also confirmed by Logistic/Cox regression analysis. Functional studies revealed the antiproliferative and pro‐apoptotic effects of DLX5 in MDS‐derived AML cell‐line SKM‐1. Finally, bioinformatics analysis demonstrated that DLX5 functioned in leukemogenesis may be through the association with PI3K/Akt signaling pathway. Collectively, our findings demonstrated that DLX5 methylation, negatively correlated DLX5 expression, was a potential prognostic and predictive indicator in patients with AML and MDS, which could also act as an epigenetic driver in myeloid neoplasms. |
format | Online Article Text |
id | pubmed-7403826 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74038262020-08-06 Identification and validation of prognosis‐related DLX5 methylation as an epigenetic driver in myeloid neoplasms Zhang, Ting‐juan Xu, Zi‐jun Gu, Yu Wen, Xiang‐mei Ma, Ji‐chun Zhang, Wei Deng, Zhao‐qun Leng, Jia‐yan Qian, Jun Lin, Jiang Zhou, Jing‐dong Clin Transl Med Research Articles The deregulated DLX gene family members DLX1/2/3/4/5/6 (DLXs) caused by DNA methylation has been demonstrated in various cancers with therapeutic target value. However, the potential role of DLXs methylation in myeloid neoplasms such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) remains to be elucidated. Clinical significance of DLXs methylation/expression was analyzed in patient with AML and MDS. The functional roles of DLXs were determined in vitro. In the identification stage, we found that lower DLX5 expression was correlated with prognosis in AML among all DLXs analyzed by The Cancer Genome Atlas datasets. In the validation stage, we revealed that reduced DLX5 expression was frequently occurred, and was also correlated with promoter hypermethylation in AML evaluated by targeted bisulfite sequencing. Epigenetic studies also showed that DLX5 promoter DNA methylation was associated with its expression. By quantitative polymerase chain reaction, we also validated that DLX5 hypermethylation was frequent event in both AML and MDS, and also correlated with MDS transformation to leukemia. Moreover, DLX5 hypermethylation was associated with lower rate of complete remission and shorter time of leukemia‐free/overall survival, and was also confirmed by Logistic/Cox regression analysis. Functional studies revealed the antiproliferative and pro‐apoptotic effects of DLX5 in MDS‐derived AML cell‐line SKM‐1. Finally, bioinformatics analysis demonstrated that DLX5 functioned in leukemogenesis may be through the association with PI3K/Akt signaling pathway. Collectively, our findings demonstrated that DLX5 methylation, negatively correlated DLX5 expression, was a potential prognostic and predictive indicator in patients with AML and MDS, which could also act as an epigenetic driver in myeloid neoplasms. John Wiley and Sons Inc. 2020-06-04 /pmc/articles/PMC7403826/ /pubmed/32508046 http://dx.doi.org/10.1002/ctm2.29 Text en © 2020 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Zhang, Ting‐juan Xu, Zi‐jun Gu, Yu Wen, Xiang‐mei Ma, Ji‐chun Zhang, Wei Deng, Zhao‐qun Leng, Jia‐yan Qian, Jun Lin, Jiang Zhou, Jing‐dong Identification and validation of prognosis‐related DLX5 methylation as an epigenetic driver in myeloid neoplasms |
title | Identification and validation of prognosis‐related DLX5 methylation as an epigenetic driver in myeloid neoplasms |
title_full | Identification and validation of prognosis‐related DLX5 methylation as an epigenetic driver in myeloid neoplasms |
title_fullStr | Identification and validation of prognosis‐related DLX5 methylation as an epigenetic driver in myeloid neoplasms |
title_full_unstemmed | Identification and validation of prognosis‐related DLX5 methylation as an epigenetic driver in myeloid neoplasms |
title_short | Identification and validation of prognosis‐related DLX5 methylation as an epigenetic driver in myeloid neoplasms |
title_sort | identification and validation of prognosis‐related dlx5 methylation as an epigenetic driver in myeloid neoplasms |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403826/ https://www.ncbi.nlm.nih.gov/pubmed/32508046 http://dx.doi.org/10.1002/ctm2.29 |
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