Activating mutations affecting other signaling effectors, such as NRAS, KRAS, KIT, FLT3, and PTPN11, are also frequently found and are often mutually exclusive with JAK2 mutations, highlighting the high incidence (>60%) of constitutively active signaling pathways in DS–ALL [67, 72]. Here, FLT3 is linked to acute lymphoblastic leukemia.