Wulferta M et al. – Acquired mtDNA mutations appear in high frequency in myelodysplastic syndrome (MDS), although their functional importance is unclear; clonally expanded mitochondrial DNA (mtDNA) mutations in MDS support the concept of age-related damage to mtDNA in hematopoietic stem cells Methods
Study of frequency and spectrum of mtDNA somatic mutations in bone marrow on MDS pts
Review of 104 MDS pts: refractory anemia in 24 and in 32 with ringed sideroblasts, 34 excess of blasts, 7 excess blasts in transformation to acute leukemia; chronic myelo-monocytic leukemia in 7; acute myeloid leukemia in 3; myeloproliferative disease in 36 pts
Heteroduplex analysis with denaturing high-performance liquid chromatography (dHPLC) for mutation scanning
Amplification of entire mitochondrial genome in 67 overlapping polymerase chain reaction fragments
DNA sequencing to confirm abnormal dHPLC findings
Results
Heteroplasmic mtDNA mutations, mostly transitions, in 56% of MDS and 44% of myeloproliferative disorder pts
Mutation frequency increased with age and advanced disease in MDS
Mutational spectra: no hot spots; similar in different types of MDS
Heteroplasmic mutations were not known polymorphisms; ~50% affected conserved amino acids or nucleotides
Mutations less frequent in protein-encoding genes vs other mitochondrial genes
See all
