MtDNA Sequence of MDS Patients Treated with CoQ10.

We conducted a pilot study to test the efficacy of coQ10 in improving the cytopenias of MDS patients with low to intermediate risk MDS. Almost every patient experienced a reduction in fatigue and improvement in life quality. Among 25 evaluable patients, 7 responded according to the International Working Group (IWG) criteria. Responses included two trilineage and 1 monolineage response, two cytogenetic responses, and two patients showed a change in FAB type from CMMoL to RA and RARS. CoQ10 is an important coenzyme that has been shown to be involved in protection against oxidative stress, inhibition of apoptosis, and generation of ATP. Mutations in mitochondrial DNA have previously been found in MDS patients. We hypothesized that acquired mutations in the mitochondrial genome may relate to the efficacy of coQ10 treatment. We therefore sequenced the mitochondrial genome (mtDNA) of 9 patients, including 4 responders and 5 nonresponders, and 2 normal samples to determine if differences in the frequency or location of mtDNA mutations could be correlated to response. Whole genomic DNA was isolated from bone marrow monocytes and the mtDNA was PCR amplified in 40 overlapping segments. The PCR products were then sequenced and compared to a mitochondrial genome database (www.mitomap.org) to identify mutations. This technique will not detect mutations present in only a small subset of DNA copies. However, mutations present in a majority of mtDNA that may directly contribute to the expansion of the MDS clone will be identified. Interestingly, although mutations were observed, no differences were found that distinguished responders from nonresponders. We conclude from this analysis that the clinical benefit to MDS patients is not related to specific mutations in the mitochondrial genome. Clinical response may instead be related to other pleiotropic effects of coQ10, such as inhibition of apoptosis.