title: Clinicopathological Implications of Mitochondrial Genome Alterations in Pediatric Acute Myeloid Leukemia.
abstract: BACKGROUND
  To the best of our knowledge, the association between pediatric AML and mitochondrial aberrations has not been studied. We investigated various mitochondrial aberrations in pediatric AML and evaluated their impact on clinical outcomes.
  
  
  METHODS
  Sequencing, mitochondrial DNA (mtDNA) copy number determination, mtDNA 4,977-bp large deletion assessments, and gene scan analyses were performed on the bone marrow mononuclear cells of 55 pediatric AML patients and on the peripheral blood mononuclear cells of 55 normal controls. Changes in the mitochondrial mass, mitochondrial membrane potential, and intracellular reactive oxygen species (ROS) levels were also examined.
  
  
  RESULTS
  mtDNA copy numbers were about two-fold higher in pediatric AML cells than in controls (P<0.0001). Furthermore, a close relationship was found between mtDNA copy number tertiles and the risk of pediatric AML. Intracellular ROS levels, mitochondrial mass, and mitochondrial membrane potentials were all elevated in pediatric AML. The frequency of the mtDNA 4,977-bp large deletion was significantly higher (P<0.01) in pediatric AML cells, and pediatric AML patients harboring high amount of mtDNA 4,977-bp deletions showed shorter overall survival and event-free survival rates, albeit without statistical significance.
  
  
  CONCLUSIONS
  The present findings demonstrate an association between mitochondrial genome alterations and the risk of pediatric AML.
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea.|Brain Korea 21 Plus Project, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Min-Gu
authors.initials: MG
authors.lastname: Kang
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea.|Department of Pediatrics, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea.
authors.forename: Yu-Na
authors.initials: YN
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea.
authors.forename: Jun Hyung
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Cell Therapy, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Szardenings
authors.affiliation: Department of Pediatrics, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea.|Environmental Health Center for Childhood Leukemia and Cancer, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea.
authors.forename: Hee-Jo
authors.initials: HJ
authors.lastname: Baek
authors.affiliation: Department of Pediatrics, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea.|Environmental Health Center for Childhood Leukemia and Cancer, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea.
authors.forename: Hoon
authors.initials: H
authors.lastname: Kook
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea.|College of Korean Medicine, Dongshin University, Naju, Korea, Korea. 98lani@gmail.com.
authors.forename: Hye-Ran
authors.initials: HR
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea.|Environmental Health Center for Childhood Leukemia and Cancer, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea.|Brain Korea 21 Plus Project, Chonnam National University Medical School, Gwangju, Korea. mgshin@chonnam.ac.kr.
authors.forename: Myung-Geun
authors.initials: MG
authors.lastname: Shin
mesh_terms: D001854:Bone Marrow Cells / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D017353:Gene Deletion; D018628:Gene Dosage; D054629:Genome, Mitochondrial; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D053078:Membrane Potential, Mitochondrial; D018598:Minisatellite Repeats / Q000235:genetics; D016017:Odds Ratio; D017382:Reactive Oxygen Species / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015996:Survival Rate
chemical_list: D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species
keywords: 4,977-bp deletion; Acute myeloid leukemia; Clinical outcomes; Copy number; Pediatric; mtDNA