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Zinc finger protein 382 is downregulated by promoter hypermethylation in pediatric acute myeloid leukemia patients

Acute myeloid leukemia (AML) is the second-most common form of leukemia in children. Aberrant DNA methylation patterns are characteristic of AML. Zinc finger protein 382 (ZNF382) has been suggested to be a tumor suppressor gene possibly regulated by promoter hypermethylation in various types of huma...

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Autores principales: TAO, YAN-FANG, HU, SHAO-YAN, LU, JUN, CAO, LAN, ZHAO, WEN-LI, XIAO, PEI-FANG, XU, LI-XIAO, LI, ZHI-HENG, WANG, NA-NA, DU, XIAO-JUAN, SUN, LI-CHAO, ZHAO, HE, FANG, FANG, SU, GUANG-HAO, LI, YAN-HONG, LI, YI-PING, XU, YUN-YUN, NI, JIAN, WANG, JIAN, FENG, XING, PAN, JIAN
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214337/
https://www.ncbi.nlm.nih.gov/pubmed/25319049
http://dx.doi.org/10.3892/ijmm.2014.1966
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author TAO, YAN-FANG
HU, SHAO-YAN
LU, JUN
CAO, LAN
ZHAO, WEN-LI
XIAO, PEI-FANG
XU, LI-XIAO
LI, ZHI-HENG
WANG, NA-NA
DU, XIAO-JUAN
SUN, LI-CHAO
ZHAO, HE
FANG, FANG
SU, GUANG-HAO
LI, YAN-HONG
LI, YI-PING
XU, YUN-YUN
NI, JIAN
WANG, JIAN
FENG, XING
PAN, JIAN
author_facet TAO, YAN-FANG
HU, SHAO-YAN
LU, JUN
CAO, LAN
ZHAO, WEN-LI
XIAO, PEI-FANG
XU, LI-XIAO
LI, ZHI-HENG
WANG, NA-NA
DU, XIAO-JUAN
SUN, LI-CHAO
ZHAO, HE
FANG, FANG
SU, GUANG-HAO
LI, YAN-HONG
LI, YI-PING
XU, YUN-YUN
NI, JIAN
WANG, JIAN
FENG, XING
PAN, JIAN
author_sort TAO, YAN-FANG
collection PubMed
description Acute myeloid leukemia (AML) is the second-most common form of leukemia in children. Aberrant DNA methylation patterns are characteristic of AML. Zinc finger protein 382 (ZNF382) has been suggested to be a tumor suppressor gene possibly regulated by promoter hypermethylation in various types of human cancer. However, ZNF382 expression and methylation status in pediatric AML is unknown. In the present study, ZNF382 transcription levels were evaluated by quantitative reverse-transcription PCR. Methylation status was investigated by methylation-specific (MSP) PCR and bisulfate genomic sequencing (BGS). The prognostic significance of ZNF382 expression and promoter methylation was assessed in 105 cases of pediatric AML. The array data suggested that the ZNF382 promoter was hypermethylated in the AML cases examined. MSP PCR and BGS analysis revealed that ZNF382 was hypermethylated in leukemia cell lines. Furthermore, treatment with 5-aza-2′-deoxycytidine (5-Aza) upregulated ZNF382 expression in the selected leukemia cell lines. The aberrant methylation of ZNF382 was observed in 10% (2/20) of the control samples compared with 26.7% (28/105) of the AML samples. ZNF382 expression was significantly decreased in the 105 AML patients compared with the controls. Patients with ZNF382 methylation showed lower ZNF382 transcript levels compared with patients exhibiting no methylation. There were no significant differences in clinical characteristics or cytogenetic analysis between the patients with or without ZNF382 methylation. ZNF382 methylation correlated with minimal residual disease (MRD). Kaplan-Meier survival analysis revealed similar survival times in the samples with ZNF382 methylation, and multivariate analysis revealed that ZNF382 methylation was not an independent prognostic factor in pediatric AML. The epigenetic inactivation of ZNF382 by promoter hypermethylation can be observed in AML cell lines and pediatric AML samples. Therefore, our study suggests that ZNF382 may be considered a putative tumor suppressor gene in pediatric AML. However, further studies focusing on the mechanisms responsible for ZNF382 downregulation in pediatric leukemia are required.
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spelling pubmed-42143372014-10-30 Zinc finger protein 382 is downregulated by promoter hypermethylation in pediatric acute myeloid leukemia patients TAO, YAN-FANG HU, SHAO-YAN LU, JUN CAO, LAN ZHAO, WEN-LI XIAO, PEI-FANG XU, LI-XIAO LI, ZHI-HENG WANG, NA-NA DU, XIAO-JUAN SUN, LI-CHAO ZHAO, HE FANG, FANG SU, GUANG-HAO LI, YAN-HONG LI, YI-PING XU, YUN-YUN NI, JIAN WANG, JIAN FENG, XING PAN, JIAN Int J Mol Med Articles Acute myeloid leukemia (AML) is the second-most common form of leukemia in children. Aberrant DNA methylation patterns are characteristic of AML. Zinc finger protein 382 (ZNF382) has been suggested to be a tumor suppressor gene possibly regulated by promoter hypermethylation in various types of human cancer. However, ZNF382 expression and methylation status in pediatric AML is unknown. In the present study, ZNF382 transcription levels were evaluated by quantitative reverse-transcription PCR. Methylation status was investigated by methylation-specific (MSP) PCR and bisulfate genomic sequencing (BGS). The prognostic significance of ZNF382 expression and promoter methylation was assessed in 105 cases of pediatric AML. The array data suggested that the ZNF382 promoter was hypermethylated in the AML cases examined. MSP PCR and BGS analysis revealed that ZNF382 was hypermethylated in leukemia cell lines. Furthermore, treatment with 5-aza-2′-deoxycytidine (5-Aza) upregulated ZNF382 expression in the selected leukemia cell lines. The aberrant methylation of ZNF382 was observed in 10% (2/20) of the control samples compared with 26.7% (28/105) of the AML samples. ZNF382 expression was significantly decreased in the 105 AML patients compared with the controls. Patients with ZNF382 methylation showed lower ZNF382 transcript levels compared with patients exhibiting no methylation. There were no significant differences in clinical characteristics or cytogenetic analysis between the patients with or without ZNF382 methylation. ZNF382 methylation correlated with minimal residual disease (MRD). Kaplan-Meier survival analysis revealed similar survival times in the samples with ZNF382 methylation, and multivariate analysis revealed that ZNF382 methylation was not an independent prognostic factor in pediatric AML. The epigenetic inactivation of ZNF382 by promoter hypermethylation can be observed in AML cell lines and pediatric AML samples. Therefore, our study suggests that ZNF382 may be considered a putative tumor suppressor gene in pediatric AML. However, further studies focusing on the mechanisms responsible for ZNF382 downregulation in pediatric leukemia are required. D.A. Spandidos 2014-12 2014-10-13 /pmc/articles/PMC4214337/ /pubmed/25319049 http://dx.doi.org/10.3892/ijmm.2014.1966 Text en Copyright © 2014, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
TAO, YAN-FANG
HU, SHAO-YAN
LU, JUN
CAO, LAN
ZHAO, WEN-LI
XIAO, PEI-FANG
XU, LI-XIAO
LI, ZHI-HENG
WANG, NA-NA
DU, XIAO-JUAN
SUN, LI-CHAO
ZHAO, HE
FANG, FANG
SU, GUANG-HAO
LI, YAN-HONG
LI, YI-PING
XU, YUN-YUN
NI, JIAN
WANG, JIAN
FENG, XING
PAN, JIAN
Zinc finger protein 382 is downregulated by promoter hypermethylation in pediatric acute myeloid leukemia patients
title Zinc finger protein 382 is downregulated by promoter hypermethylation in pediatric acute myeloid leukemia patients
title_full Zinc finger protein 382 is downregulated by promoter hypermethylation in pediatric acute myeloid leukemia patients
title_fullStr Zinc finger protein 382 is downregulated by promoter hypermethylation in pediatric acute myeloid leukemia patients
title_full_unstemmed Zinc finger protein 382 is downregulated by promoter hypermethylation in pediatric acute myeloid leukemia patients
title_short Zinc finger protein 382 is downregulated by promoter hypermethylation in pediatric acute myeloid leukemia patients
title_sort zinc finger protein 382 is downregulated by promoter hypermethylation in pediatric acute myeloid leukemia patients
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214337/
https://www.ncbi.nlm.nih.gov/pubmed/25319049
http://dx.doi.org/10.3892/ijmm.2014.1966
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