Hypomethylation of MIR‐378 5’‐flanking region predicts poor survival in young patients with myelodysplastic syndrome
Abstract Background Previous studies have disclosed up‐regulation of MIR‐378 in acute myeloid leukemia (AML), and might consequently affect the outcome of the patients. Correspondingly, hypomethylation of MIR‐378 was also identified in AML, particularly for FAB‐M2 subtype with t(8;21) chromosomal tr...
Main Authors: | , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2020-01-01
|
Series: | Molecular Genetics & Genomic Medicine |
Subjects: | |
Online Access: | https://doi.org/10.1002/mgg3.1067 |
_version_ | 1797987142059687936 |
---|---|
author | De‐hong Wu Xiao‐wen Zhu Xiang‐mei Wen Ying‐ying Zhang Ji‐chun Ma Dong‐ming Yao Jing‐dong Zhou Hong Guo Peng‐fei Wu Xing‐li Zhang Hong‐chun Qiu Jiang Lin Jun Qian |
author_facet | De‐hong Wu Xiao‐wen Zhu Xiang‐mei Wen Ying‐ying Zhang Ji‐chun Ma Dong‐ming Yao Jing‐dong Zhou Hong Guo Peng‐fei Wu Xing‐li Zhang Hong‐chun Qiu Jiang Lin Jun Qian |
author_sort | De‐hong Wu |
collection | DOAJ |
description | Abstract Background Previous studies have disclosed up‐regulation of MIR‐378 in acute myeloid leukemia (AML), and might consequently affect the outcome of the patients. Correspondingly, hypomethylation of MIR‐378 was also identified in AML, particularly for FAB‐M2 subtype with t(8;21) chromosomal translocation. Nevertheless, the methylation status of MIR‐378 has not been illustrated in myelodysplastic syndrome (MDS). Herein we designed to understand the methylation pattern of MIR‐378 involved in MDS and clinical interrelation thereof. Methods Real‐time quantitative methylation‐specific PCR (RQ‐MSP) was performed to evaluate the methylation degree of MIR‐378 5’‐flanking region on bone marrow mononuclear cells collected from 95 de novo MDS patients. Five gene mutations (IDH1, IDH2, DNMT3A, U2AF1, and SF3B1) were detected by high‐resolution melting analysis to further evaluate the clinical relevance of hypomethylation of MIR‐378. Results Unmethylated level of MIR‐378 5’‐flanking region was significantly higher in MDS patients than that in controls (p = .034). Hypomethylated MIR‐378 was identified in 20 of 95 (21%) cases with MDS. Male patients appeared to be more frequent to harbor MIR‐378 hypomethylation compared to female patients (15/55, 27.3% vs. 4/40, 10.0%, p = .04). There was no significant difference in age, white blood cell counts, platelet counts, hemoglobin concentration, and karyotypes between the patients with and without MIR‐378‐hypomethylation. Distinct distribution of five gene mutations was not observed in the two groups as well. However, MIR‐378‐hypomethylated patients had significantly shorter overall survival than those without MIR‐378 hypomethylation (p = .036). Moreover, among patients <60 years, hypomethylation of MIR‐378 was confirmed to be an independent adverse prognostic factor by both Kaplan–Meier and Multivariate Cox analyses. Conclusion Hypomethylation of MIR‐378 5’‐flanking region is an adverse prognosticator in MDS, particularly in patients <60 years. |
first_indexed | 2024-04-11T07:43:55Z |
format | Article |
id | doaj.art-6866edc467ea48f0a9a0f583f693bad8 |
institution | Directory Open Access Journal |
issn | 2324-9269 |
language | English |
last_indexed | 2024-04-11T07:43:55Z |
publishDate | 2020-01-01 |
publisher | Wiley |
record_format | Article |
series | Molecular Genetics & Genomic Medicine |
spelling | doaj.art-6866edc467ea48f0a9a0f583f693bad82022-12-22T04:36:24ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-01-0181n/an/a10.1002/mgg3.1067Hypomethylation of MIR‐378 5’‐flanking region predicts poor survival in young patients with myelodysplastic syndromeDe‐hong Wu0Xiao‐wen Zhu1Xiang‐mei Wen2Ying‐ying Zhang3Ji‐chun Ma4Dong‐ming Yao5Jing‐dong Zhou6Hong Guo7Peng‐fei Wu8Xing‐li Zhang9Hong‐chun Qiu10Jiang Lin11Jun Qian12Department of Hematology Affiliated People’s Hospital of Jiangsu University Zhenjiang Jiangsu People’s Republic of ChinaDepartment of Hematology Affiliated People’s Hospital of Jiangsu University Zhenjiang Jiangsu People’s Republic of ChinaLaboratory Center Affiliated People’s Hospital of Jiangsu University Zhenjiang Jiangsu People’s Republic of ChinaDepartment of Hematology Affiliated People’s Hospital of Jiangsu University Zhenjiang Jiangsu People’s Republic of ChinaLaboratory Center Affiliated People’s Hospital of Jiangsu University Zhenjiang Jiangsu People’s Republic of ChinaLaboratory Center Affiliated People’s Hospital of Jiangsu University Zhenjiang Jiangsu People’s Republic of ChinaDepartment of Hematology Affiliated People’s Hospital of Jiangsu University Zhenjiang Jiangsu People’s Republic of ChinaLaboratory Center Affiliated People’s Hospital of Jiangsu University Zhenjiang Jiangsu People’s Republic of ChinaDepartment of Hematology Kunshan Third People’s Hospital KunShan Jiangsu People’s Republic of ChinaDepartment of Hematology Kunshan Third People’s Hospital KunShan Jiangsu People’s Republic of ChinaDepartment of Hematology Kunshan Third People’s Hospital KunShan Jiangsu People’s Republic of ChinaLaboratory Center Affiliated People’s Hospital of Jiangsu University Zhenjiang Jiangsu People’s Republic of ChinaDepartment of Hematology Affiliated People’s Hospital of Jiangsu University Zhenjiang Jiangsu People’s Republic of ChinaAbstract Background Previous studies have disclosed up‐regulation of MIR‐378 in acute myeloid leukemia (AML), and might consequently affect the outcome of the patients. Correspondingly, hypomethylation of MIR‐378 was also identified in AML, particularly for FAB‐M2 subtype with t(8;21) chromosomal translocation. Nevertheless, the methylation status of MIR‐378 has not been illustrated in myelodysplastic syndrome (MDS). Herein we designed to understand the methylation pattern of MIR‐378 involved in MDS and clinical interrelation thereof. Methods Real‐time quantitative methylation‐specific PCR (RQ‐MSP) was performed to evaluate the methylation degree of MIR‐378 5’‐flanking region on bone marrow mononuclear cells collected from 95 de novo MDS patients. Five gene mutations (IDH1, IDH2, DNMT3A, U2AF1, and SF3B1) were detected by high‐resolution melting analysis to further evaluate the clinical relevance of hypomethylation of MIR‐378. Results Unmethylated level of MIR‐378 5’‐flanking region was significantly higher in MDS patients than that in controls (p = .034). Hypomethylated MIR‐378 was identified in 20 of 95 (21%) cases with MDS. Male patients appeared to be more frequent to harbor MIR‐378 hypomethylation compared to female patients (15/55, 27.3% vs. 4/40, 10.0%, p = .04). There was no significant difference in age, white blood cell counts, platelet counts, hemoglobin concentration, and karyotypes between the patients with and without MIR‐378‐hypomethylation. Distinct distribution of five gene mutations was not observed in the two groups as well. However, MIR‐378‐hypomethylated patients had significantly shorter overall survival than those without MIR‐378 hypomethylation (p = .036). Moreover, among patients <60 years, hypomethylation of MIR‐378 was confirmed to be an independent adverse prognostic factor by both Kaplan–Meier and Multivariate Cox analyses. Conclusion Hypomethylation of MIR‐378 5’‐flanking region is an adverse prognosticator in MDS, particularly in patients <60 years.https://doi.org/10.1002/mgg3.1067hypomethylationMIR‐378myelodysplastic syndromeprognosis |
spellingShingle | De‐hong Wu Xiao‐wen Zhu Xiang‐mei Wen Ying‐ying Zhang Ji‐chun Ma Dong‐ming Yao Jing‐dong Zhou Hong Guo Peng‐fei Wu Xing‐li Zhang Hong‐chun Qiu Jiang Lin Jun Qian Hypomethylation of MIR‐378 5’‐flanking region predicts poor survival in young patients with myelodysplastic syndrome Molecular Genetics & Genomic Medicine hypomethylation MIR‐378 myelodysplastic syndrome prognosis |
title | Hypomethylation of MIR‐378 5’‐flanking region predicts poor survival in young patients with myelodysplastic syndrome |
title_full | Hypomethylation of MIR‐378 5’‐flanking region predicts poor survival in young patients with myelodysplastic syndrome |
title_fullStr | Hypomethylation of MIR‐378 5’‐flanking region predicts poor survival in young patients with myelodysplastic syndrome |
title_full_unstemmed | Hypomethylation of MIR‐378 5’‐flanking region predicts poor survival in young patients with myelodysplastic syndrome |
title_short | Hypomethylation of MIR‐378 5’‐flanking region predicts poor survival in young patients with myelodysplastic syndrome |
title_sort | hypomethylation of mir 378 5 flanking region predicts poor survival in young patients with myelodysplastic syndrome |
topic | hypomethylation MIR‐378 myelodysplastic syndrome prognosis |
url | https://doi.org/10.1002/mgg3.1067 |
work_keys_str_mv | AT dehongwu hypomethylationofmir3785flankingregionpredictspoorsurvivalinyoungpatientswithmyelodysplasticsyndrome AT xiaowenzhu hypomethylationofmir3785flankingregionpredictspoorsurvivalinyoungpatientswithmyelodysplasticsyndrome AT xiangmeiwen hypomethylationofmir3785flankingregionpredictspoorsurvivalinyoungpatientswithmyelodysplasticsyndrome AT yingyingzhang hypomethylationofmir3785flankingregionpredictspoorsurvivalinyoungpatientswithmyelodysplasticsyndrome AT jichunma hypomethylationofmir3785flankingregionpredictspoorsurvivalinyoungpatientswithmyelodysplasticsyndrome AT dongmingyao hypomethylationofmir3785flankingregionpredictspoorsurvivalinyoungpatientswithmyelodysplasticsyndrome AT jingdongzhou hypomethylationofmir3785flankingregionpredictspoorsurvivalinyoungpatientswithmyelodysplasticsyndrome AT hongguo hypomethylationofmir3785flankingregionpredictspoorsurvivalinyoungpatientswithmyelodysplasticsyndrome AT pengfeiwu hypomethylationofmir3785flankingregionpredictspoorsurvivalinyoungpatientswithmyelodysplasticsyndrome AT xinglizhang hypomethylationofmir3785flankingregionpredictspoorsurvivalinyoungpatientswithmyelodysplasticsyndrome AT hongchunqiu hypomethylationofmir3785flankingregionpredictspoorsurvivalinyoungpatientswithmyelodysplasticsyndrome AT jianglin hypomethylationofmir3785flankingregionpredictspoorsurvivalinyoungpatientswithmyelodysplasticsyndrome AT junqian hypomethylationofmir3785flankingregionpredictspoorsurvivalinyoungpatientswithmyelodysplasticsyndrome |