While early studies focused solely on mutations in NRAS and KRAS, more comprehensive screens with inclusion of additional genes impacting on the pathway, including PTPN11, FLT3, and CBL, report mutations in up to 35% of newly diagnosed ALL, with a predominance in B lineage ALL (9–11, 13, 14, 16, 18–20, 32, 72–74). The gene discussed is PTPN11; the disease is acute lymphoblastic leukemia.