Relationship between unexplained cytopenias and mutations. (A) Multiple mutations at high variant allele frequency indicate a clone of substantial size and suggest a high likelihood of a myeloid neoplasm, whereas single mutations at low variant allele frequency is more likely to be CHIP, but the threshold between these states is currently unclear. (B) Venn diagram of the intersection of morphologic dysplasia, clonal mutations and peripheral blood cytopenias. In the future, some patients with cytopenias plus clonal mutations, currently designated as CCUS, may be redefined as MDS. Patients with dysplasia and cytopenias without mutations, in contrast, although currently defined as MDS, may be found to have a distinct syndrome. Such patients appear to be overrepresented in series of responders to immunosuppressive therapy, for example. IDUS, idiopathic dysplasia of undetermined significance.