Gattermann Figure 6 (in Greenberg et al). Proposed model of MDS pathogenesis including mitochondrial pathology.

With advancing age, hematopoietic stem cells accumulate mutations of mitochondrial DNA (mtDNA). If a stem cell with mutant mtDNA becomes transformed by additional mutations in the cell nucleus, a clonal bone marrow can be established and the clinical picture of MDS can arise. MtDNA mutations may play a major role in shaping the phenotype of the MDS clone, as exemplified by the formation of ringed sideroblasts. In addition, by contributing to genomic instability, mtDNA mutations may facilitate the transforming event that initiates an MDS clone and may also promote further chromosomal changes which drive the clonal evolution towards leukemia.