Detection of prognostic methylation markers by methylC-capture sequencing in acute myeloid leukemia
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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
Li Yu, email: firstname.lastname@example.org
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
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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