Subtypes with mutations in PTPN11, NRAS and KRAS, are characterized by heterozygous somatic gain of function mutations, while JMML harboring mutations in NF1 or CBL are defined by germline RAS disease and acquired biallelic inactivation of respective genes in hematopoietic cells [22]. This evidence concerns the gene CBL and juvenile myelomonocytic leukemia.