In general, MDS/MPN frequently harbor mutations resulting in hyperactivation of the RAS/MAPK pathway (primarily CBL, KRAS, NRAS or PTPN11) [11,12,13], as well as mutations in epigenetic modifiers (most commonly ASXL1 or TET2) [14,15,16,17] and splicing factors (SRSF2 mutations being present in nearly half of chronic myelomonocytic leukemia (CMML) cases) [18], often combined with a MPN-characteristic driver mutation, as mentioned above. The gene discussed is CBL; the disease is chronic myelomonocytic leukemia.