In fact, a proportion of individuals with CH driven by mutations in splicing or signal transduction pathways who progress to MDS or MPN appear to do so without acquiring a further driver event: for example, approximately one-quarter of SF3B1-mutated MDS cases display no additional driver mutations (141), and 45% of MPNs bear only a single driver, namely mutant JAK2, CALR, or MPL (143). This evidence concerns the gene CALR and cyclic hematopoiesis.