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Prepublished online as a Blood First Edition Paper on November 21, 2002; DOI 10.1182/blood-2002-06-1825.
Submitted June 20, 2002
Accepted November 12, 2002
Mitochondrial DNA mutations in patients with myelodysplastic syndromes
Myung Geun Shin, Sachiko Kajigaya, Barbara C Levin, and Neal S Young*
Hematology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
Biotechnology Division, National Institutes of Standards and Technology, Gaithersburg, MD, USA
* Corresponding author; email: youngn{at}nhlbi.nih.gov.
We undertook to systematically analyze the entire mitochondrial genome by gene amplification and direct sequencing in ten patients with myelodysplasia; results were compared with concomitantly studied eight normal volunteers as well as mtDNA sequences in accepted databases. Nucleotide changes that were present in our normal controls as well as those in published databases were counted as polymorphisms. Overall, there was no increase in the number of mtDNA genes harboring polymorphisms or 'new' mutations between our patients and normal controls, although there were a few more mtDNA changes resulting in amino acid changes in myelodysplasia (9 in 8 controls versus 16 in 10 patients). Thirty new mutations, all nucleotide substitutions, were found among the ten patients, distributed throughout the mitochondrial genome; five mutations resulted in amino acid changes, but none in the controls. We were not able to confirm previously described mutations in sideroblastic anemia, nor 'hot spots' in the cytochrome c oxidase I and II genes. Our data do not support a major role for mitochondrial genomic instability in myelodysplasia, and they fail to confirm previous reports of significant or widespread mitochondrial mutations in this disease. Modest changes in mutation numbers and mitochondrial microsatellites may be evidence of increased mutagenesis in mtDNA, or, more likely, a reflection of limited clonality among hematopoietic stem cells in this bone marrow failure syndrome.
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