Ahn Jae-Sook, Kim Hyeoung-Joon, Kim Yeo-Kyeoung, Lee Seung-Shin, Ahn Seo-Yeon, Jung Sung-Hoon, Yang Deok-Hwan, Lee Je-Jung, Park Hee Jeong, Choi Seung Hyun, Jung Chul Won, Jang Jun-Ho, Kim Hee Je, Moon Joon Ho, Sohn Sang Kyun, Won Jong-Ho, Kim Sung-Hyun, Michael Szardenings, Minden Mark D, Kim Dennis Dong Hwan
Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea.
Genomic Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea.
Oncotarget. 2017 Jan 31;8(5):8305-8314. doi: 10.18632/oncotarget.14171.
Stem cells display remarkably high levels of 5-hydroxymethylcytosine (5hmC). Both TET2 and IDH1/2 mutations can impair the production of 5hmC, thus decreasing 5hmC levels. TET2 or IDH1/2 mutations are commonly observed in acute myeloid leukemia (AML). However, the implications of 5hmC on survival in normal karyotype AML patients have not been fully evaluated. The 5hmC levels were analyzed in 375 patients using ELISA. The levels of 5hmC in DNA samples were converted to a log scale for the analysis and correlations with TET2 and/or IDH1/2 mutations were evaluated. The median 5hmC level was 0.065% (range 0.001-0.999). Mutation rates were 13.1% for TET2mut, 6.7% for IDH1mut, and 13.9% for IDH2mut. The prevalence of TET2 and/or IDH1/2 was 33.1% (124/375). TET2 and IDH1/2 mutated patients had significantly lower levels of log(5hmC) compared with patients without TET2 or IDH1/2 mutations (p<0.001). With a median follow-up of 55.5 months (range, 0.7-179.8), there was no significant difference in overall survival, event-free survival, and relapse risk according to TET2mut or IDH1/2mut (all, p>0.05). To identify its prognostic value, we sub-classified the levels of 5hmC into tertiles for 5hmC values. However, there was no significant association between the categories of 5hmC levels and survival or relapse risk (all p>0.05). Patients with TET2 or IDH1/2 mutations had lower levels of 5hmC. The 5hmC levels may not be predictive of survival in patients with normal karyotype AML.
干细胞表现出显著高水平的5-羟甲基胞嘧啶（5hmC）。TET2和IDH1/2突变均可损害5hmC的产生，从而降低5hmC水平。TET2或IDH1/2突变在急性髓系白血病（AML）中普遍存在。然而，5hmC对正常核型AML患者生存的影响尚未得到充分评估。采用酶联免疫吸附测定（ELISA）分析了375例患者的5hmC水平。将DNA样本中的5hmC水平转换为对数尺度进行分析，并评估其与TET2和/或IDH1/2突变的相关性。5hmC水平的中位数为0.065%（范围0.001 - 0.999）。TET2突变率为13.1%，IDH1突变为6.7%，IDH2突变为13.9%。TET2和/或IDH1/2的发生率为33.1%（124/375）。与未发生TET2或IDH1/2突变的患者相比，发生TET2和IDH1/2突变的患者log(5hmC)水平显著更低（p<0.001）。中位随访时间为55.5个月（范围0.7 - 179.8），根据TET2突变或IDH1/2突变情况，总生存期、无事件生存期和复发风险均无显著差异（均为p>0.05）。为确定其预后价值，我们将5hmC水平分为三分位数。然而，5hmC水平类别与生存或复发风险之间无显著关联（均为p>0.05）。发生TET2或IDH1/2突变的患者5hmC水平较低。5hmC水平可能无法预测正常核型AML患者的生存情况。
