Invariant Patterns of Clonal Succession Determine Specific Clinical Features of Myelodysplastic Syndromes (MDS)

Myelodysplastic Syndromes (MDS) are heterogeneous myeloid neoplasms, characterized by stepwise acquisitions of multiple somatic mutations. Mutational configurations (e.g. bi-allelic) and specific distributions, timing of acquisitions corresponding to rank within the clonal hierarchy, and combinatorial spectrum are not elucidated. Therefore, we conducted targeted deep sequencing in a panel of the 36 most frequently mutated "myeloid" genes in terms more than of 500 patients with MDS or related myeloid neoplasms.]]> All patients with a presumed diagnosis of MDS, MDS/MPN and secondary AML (sAML) from MDS or MDS/MPN were eligible of specimen collection on this study. Patients with the histories of any chemotherapy or radiation therapy for other cancers were excluded.]]> All samples were obtained according to the Declaration of Helsinki. All patients gave written informed consent, according to protocols approved by the Institutional Review Board of participating institutions (Cleveland Clinic's Institutional Review Board (IRB) and IRB-5024).]]>