Oncotarget

Research Papers:

Detection of prognostic methylation markers by methylC-capture sequencing in acute myeloid leukemia

Yan Li, Hongmei Zhao, Qingyu Xu, Na Lv, Yu Jing, Lili Wang, Xiaowen Wang, Jing Guo, Lei Zhou, Jing Liu, Guofeng Chen, Chongjian Chen, Yonghui Li and Li Yu _

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Oncotarget. 2017; 8:110444-110459. https://doi.org/10.18632/oncotarget.22789

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Abstract

Yan Li1,2,*, Hongmei Zhao3,*, Qingyu Xu1,4,*, Na Lv1,5, Yu Jing1, Lili Wang1, Xiaowen Wang3, Jing Guo3, Lei Zhou1, Jing Liu1, Guofeng Chen1,4, Chongjian Chen3, Yonghui Li1 and Li Yu1,5

1Department of Hematology and BMT Center, Chinese PLA General Hospital, Beijing 100853, China

2Department of Hematology, Hainan Branch of Chinese PLA General Hospital, Sanya 572013, China

3Annoroad Gene Technology Co. Ltd., Beijing 100176, China

4Medical School of Nankai University, Tianjin 300071, China

5Department of Hematology, General Hospital of Shenzhen University, Shenzhen 518060, China

*These authors have contributed equally to this work

Correspondence to:

Li Yu, email: liyu301@vip.163.com

Keywords: acute myeloid leukemia; next generation sequencing; MCC-Seq; DNA methylation; prognostic markers

Received: July 19, 2017     Accepted: November 15, 2017     Published: November 30, 2017

ABSTRACT

Clinical and genetic features incompletely predict outcome in acute myeloid leukemia (AML). The value of clinical methylation assays for prognostic markers has not been extensively explored. We assess the prognostic implications of methylC-capture sequencing (MCC-Seq) in patients with de novo AML by integrating DNA methylation and genetic risk stratification. MCC-Seq assessed DNA methylation level in 44 samples. The differentially methylated regions associated with prognostic genetic information were identified. The selected prognostic DNA methylation markers were independently validated in two sets. MCC-Seq exhibited good performance in AML patients. A panel of 12 differentially methylated genes was identified with promoter hyper-differentially methylated regions associated with the outcome. Compared with a low M-value, a high M-value was associated with failure to achieve complete remission (p = 0.024), increased hazard for disease-free survival in the study set (p = 0.039) and poor overall survival in The Cancer Genome Atlas set (p = 0.038). Hematopoietic stem cell transplantation and survival outcomes were not adversely affected by a high M-value (p = 0.271). Our study establishes that MCC-Seq is a stable, reproducible, and cost-effective methylation assay in AML. A 12-gene M-value encompassing epigenetic and genetic prognostic information represented a valid prognostic marker for patients with AML.


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