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...

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Main Authors: 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
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Molecular Genetics & Genomic Medicine
Subjects:
Online Access:https://doi.org/10.1002/mgg3.1067
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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.
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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
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