Oncogenic RAS pathway is the most frequently affected signaling pathway in MDS/MPN, with recurrent mutations in NRAS, KRAS, CBL, PTPN11 and NF1. Hyperactive RAS signaling is the main driving event in JMML, which is characterized by the presence of somatic mutations in K/NRAS and PTPN11 in 50% of patients, and germline mutations in CBL and NF1 [38]. Here, CBL is linked to juvenile myelomonocytic leukemia.