Clinicopathological Implications of Mitochondrial Genome Alterations in Pediatric Acute Myeloid Leukemia.
10.3343/alm.2016.36.2.101
- Author:
Min Gu KANG
1
;
Yu Na KIM
;
Jun Hyung LEE
;
Michael SZARDENINGS
;
Hee Jo BAEK
;
Hoon KOOK
;
Hye Ran KIM
;
Myung Geun SHIN
Author Information
1. Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Hwasun, Korea. 98lani@gmail.com, mgshin@chonnam.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Pediatric;
Acute myeloid leukemia;
Clinical outcomes;
mtDNA;
Copy number;
4,977-bp deletion
- MeSH:
Bone Marrow Cells/metabolism;
Case-Control Studies;
Child;
Cohort Studies;
DNA, Mitochondrial/chemistry/genetics/metabolism;
Female;
Flow Cytometry;
Gene Deletion;
Gene Dosage;
*Genome, Mitochondrial;
Humans;
Leukemia, Myeloid, Acute/genetics/mortality/*pathology;
Male;
Membrane Potential, Mitochondrial;
Minisatellite Repeats/genetics;
Odds Ratio;
Reactive Oxygen Species/metabolism;
Sequence Analysis, DNA;
Survival Rate
- From:Annals of Laboratory Medicine
2016;36(2):101-110
- CountryRepublic of Korea
- Language:English
-
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.
