Here, we show in pCMML that acquisition of RAS pathway mutations often occurs early (NRASG12D most frequent), commonly on a background of epigenetic (TET2) and splicing gene mutations (SRSF2) and correlates with WHO-defined prognostic factors including leukocytosis, BM blasts and LT to sAML; further implying that severe forms of this disease often seen in the elderly, are also RASopathies that, contrary to JMML, develop on a background of age-related clonal alterations (clonal hematopoiesis)30. This evidence concerns the gene SRSF2 and Increased total leukocyte count.