It is now well established that the mutational landscape of MDS/MPN, which could be preceded by age-related clonal hematopoiesis of indeterminate potential (CHIP) [75], combines a small number of common somatic mutations in DNA methylation, histone modifier and splicing genes with disease-segregated mutations in signaling genes, i.e., RAS pathway mutations in proliferative CMML; JAK2, MPL and CALR mutations in MDS/MPN-RS-T; and CSF3R and RAS pathway mutations in aCML [76]. This evidence concerns the gene MPL and myeloproliferative neoplasm.