title: 5-Hydroxymethylcytosine correlates with epigenetic regulatory mutations, but may not have prognostic value in predicting survival in normal karyotype acute myeloid leukemia.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jae-Sook
authors.initials: JS
authors.lastname: Ahn
authors.affiliation: 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.
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Yeo-Kyeoung
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea.
authors.forename: Seung-Shin
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea.
authors.forename: Seo-Yeon
authors.initials: SY
authors.lastname: Ahn
authors.affiliation: Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea.
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea.
authors.forename: Deok-Hwan
authors.initials: DH
authors.lastname: Yang
authors.affiliation: Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea.
authors.forename: Je-Jung
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Genomic Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea.
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Genomic Research Center for Hematopoietic Diseases, Chonnam National University Hwasun Hospital, Jeollanam-do, Republic of Korea.
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Division of Hematology-Oncology, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Jung
authors.affiliation: Division of Hematology-Oncology, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Department of Hematology, Cancer Research Institute, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Hee Je
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Hematology-Oncology, Kyungpook National University Hospital, Daegu, Republic of Korea.
authors.forename: Joon Ho
authors.initials: JH
authors.lastname: Moon
authors.affiliation: Department of Hematology-Oncology, Kyungpook National University Hospital, Daegu, Republic of Korea.
authors.forename: Sang Kyun
authors.initials: SK
authors.lastname: Sohn
authors.affiliation: Department of Hematology-Oncology, Soon Chun Hyang University Hospital, Seoul, Republic of Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Won
authors.affiliation: Department of Hematology-Oncology, Dong-A University College of Medicine, Busan, Republic of Korea.
authors.forename: Sung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
authors.forename: Szardenings
authors.initials: S
authors.lastname: Michael
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Minden
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
authors.forename: Dennis Dong Hwan
authors.initials: DD
authors.lastname: Kim
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D049308:Dioxygenases; D018450:Disease Progression; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D044127:Epigenesis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics; D053208:Kaplan-Meier Estimate; D059785:Karyotype; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D049308:Dioxygenases; C541081:TET2 protein, human
keywords: 5hmC; AML; IDH1/2; TET2; normal karyotype