A CHIP off the old (MDS) block

A CHIP off the old (MDS) blockWhile clonal hematopoiesis (CH) is now considered a precursor to myeloid neoplasia, this concept is relatively new.Unlike other premalignant hematologic conditions, which have been recognized for decades (e.g., monoclonal gammopathy of undetermined significance [MGUS] was first characterized in the 1960s), Steensma et al. established the framework for CH in their landmark 2015 paper. 1 This work highlights the importance of DNA sequencing to our understanding of myeloid neoplasia.Over the preceding years, researchers found that >85% of MDS harbor somatic mutations in a stereotyped set of genes.Simultaneously, similar changes were identified in healthy individuals as they aged -and although these were associated with an increased risk of blood cancer development (hazard ratio [HR]=11.1),most cases did not progress. 2Given their partial overlap, it was initially unclear how to parse these phenomena.Furthermore, if the latter group had cytopenias, they would have met the criteria for myelodysplastic syndrome (MDS), leading to overdiagnosis.In this context, Steensma et al. codified a definition for CH (Figure 1) and proposed an updated diagnostic schema for MDS.By doing so, they deconvoluted the two conditions and established a myeloid disease spectrum.Recognition of CH as a distinct entity permitted more extensive investigation and led to the identification of clinical TITLE Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes.