Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell malignancies. Somatic cytogenetic and molecular aberrations and the evolution of subclonal malignant cell populations are responsible for the development and progression of MDS into acute myeloid leukemia. Within only one decade the availability of new genome-wide technologies, like next generation sequencing (NGS), has revolutionized basic research. The routine clinical use of NGS analysis together with well-established diagnostic tools, like chromosome banding analysis or fluorescence in situ hybridization, will substantially add to existing diagnostic and prognostic criteria. This comprehensive combined approach could revolutionize the way we manage patient care. However, little is known about the application of such techniques in routine diagnostics and standards for such analyses are still missing. In a recent publication from the research group, (Article DOI: 10.1002/ajh.25089) it was demonstrated that the analysis of peripheral blood cells (at diagnosis) by NGS is feasible and yields data that are equivalent to the results obtained from bone marrow cells (BMC), which is currently the gold standard for most molecular diagnostic analyses. Not longer depending on the severe and for the patient painful collection of bone marrow aspirates now it is possible to perform comprehensive genetic analysis at short intervals on peripheral blood of MDS patients to detect and closely monitor patterns/pathways of clonal evolution of the malignant cell population in a routine diagnostic setting. It is expected that the obtained data from this study will substantially add to: 1. Understand the functional relevance of identified mutations and the implications of combined mutations. 2. Condense the findings from NGS together with data from established genetic methods (conventional cytogenetics, FISH) to a comprehensive view on MDS genetics and its dynamics considering strengths and weaknesses of each component of this approach. 3. Demonstrate that peripheral blood could be an appropriate sample to perform NGS follow-up studies. In a series of very low, low and intermediate risk MDS patients from Spain it is intended to retrospectively perform NGS (targeted deep sequencing) of diagnosis and consecutive follow-up samples selecting those cases that showed signs of progression of the disease.