Mitochondrial DNA variations in myelodysplastic syndrome

There have been significant advances in the understanding of mitochondrial function and their contribution to human disease in the last few years. The myelodysplastic syndromes (MDSs) are heterogeneous group of disorders characterized by clonal proliferation of multipotent hematopoietic cells with ineffective hematopoiesis. They are often associated with evidence of mitochondrial dysfunction. Studies have shown mitochondrial DNA (mtDNA) mutations in different MDS subtypes; however, their pattern and their role in etiopathogenesis and disease progression are not yet clear. This study was undertaken to determine the frequency and spectrum of mutations of mtDNA in patients with MDS from Indian subcontinent. The entire mitochondrial genome was systematically analyzed in 21 patients and 21 age- and sex-matched controls by gene amplification and direct sequencing using 24 overlapping polymerase chain reactions. A total 37 variations were detected in the entire mitochondrial genome. Thirty-three were reported polymorphisms, one was novel polymorphism, also seen in the normal controls, and three were variations (mutations), not seen in normal controls. Three mutations were detected in four patients (20%).These were point mutations scattered over the entire mitochondrial genome including tRNAs, rRNAs, and protein genes. COI and COII are not the only spots in mtDNA where mutation may occur in MDS but tRNA, ND1, ND5, and 16S ribosomal DNA are all vulnerable to such mutations. These mutations seem to be an important component of molecular pathology of MDS. However, its role in severity and disease progression needs to be elucidated.