当前位置： SCI文献检索 > JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY期刊下所有文献 > 5-Azacytidine modulates CpG methylation levels of EZH2 and NOTCH1 in myelodysplastic syndromes.

5-Azacytidine modulates CpG methylation levels of EZH2 and NOTCH1 in myelodysplastic syndromes.

Abstract：

PURPOSE:Molecular mechanisms of response to hypomethylating agents in patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) still remain largely unknown. Therefore, the effects of 5-Azacytidine (Aza) on clonal architecture and DNA methylation were investigated in this study. METHODS:Using next-generation sequencing (NGS), 30 myeloid leukemia-associated genes were analyzed in 15 MDS/CMML patients with excellent response to Aza. Effects on methylation levels were analyzed by quantitative methylation analysis using pyrosequencing for the global methylation marker LINE-1 in patients and myeloid cell lines. Various myeloid cell lines and a healthy cohort were screened for methylation levels in 23 genes. Selected targets were verified on the MDS/CMML cohort. RESULTS:The study presented here showed a stable variant allele frequency and stable global methylation levels in responding patients. A significant demethylation of EZH2 and NOTCH1 was revealed in patients with Aza response. CONCLUSIONS:A response to Aza is not associated with eradication of malignant clones, but rather with a stabilization of the clonal architecture. We suggest changes in CpG methylation levels of EZH2 and NOTCH1 as potential targets of epigenetic response to Aza treatment which may also serve as useful biomarkers after clinical evaluation.

journal_name

J Cancer Res Clin Oncol

journal_title

Journal of cancer research and clinical oncology

authors

Gawlitza AL,Speith J,Rinke J,Sajzew R,Müller EK,Schäfer V,Hochhaus A,Ernst T

doi

10.1007/s00432-019-03016-9

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

2835-2843

issue

11

eissn

0171-5216

issn

1432-1335

pii

10.1007/s00432-019-03016-9

journal_volume

145

pub_type

杂志文章

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