Although the scientific community has accumulated convincing evidences on the role of activated FLT3, which also signals through the Ras pathway, in the development of adult KMT2A-AML2,40,46 and FLT3 has been proven a therapeutic target in both AML and ALL,47,48 the role of PI3K-RAS pathway mutations on KMT2A-driven AML and ALL is controversial. Here, RUNX3 is linked to acute lymphoblastic leukemia.