About 90% of cases belong to one of 5 groups with mutations in either PTPN11, NRAS, KRAS, CBL, or NF1. The first three subtypes (PTPN11, NRAS, KRAS) are characterized by heterozygous somatic gain-of-function mutations in non-syndromic children, while JMML in neurofibromatosis type 1 and JMML in children with CBL-syndrome are characterized by germ line RAS disease and acquired biallelic inactivation of the NF1 or CBL gene in hematopoietic cells (12, 37). This evidence concerns the gene PTPN11 and juvenile myelomonocytic leukemia.