[Clonal evolution of myelodysplastic syndromes]

By intensive efforts of sequencing a large number of genomes from patients with myelodysplastic syndromes (MDS), a comprehensive registry of driver mutations repeatedly found in MDS patients has been identified, providing us with a virtually complete spectrum of driver mutations in this disease. Importantly, significant correlations between driver mutations have been revealed, suggesting that some combinations of genetic events confer strong selective advantages on mutated stem cells. Next-generation sequencing technology has also revealed that clonal hematopoiesis is a common, age-related process, in which a somatically mutated hematopoietic precursor gives rise to a genetically distinct subpopulation in the blood. Furthermore, novel germline mutations have been identified, indicating that mutated stem cells appear long before MDS presentation. Such founding mutations are thought to be acquired and positively selected for in a well-organized manner to allow expansion of the initiating clone to compromise normal hematopoiesis, ultimately resulting in MDS and subsequent transformation into acute myeloid leukemia in many patients.