APL is also associated with the development of cooperating mutations in signaling genes; in particular, mutations in FLT3 were seen in 51% of cases (33 of 65) in 1 large cohort (8), similar to the rate of FLT3 mutations cooperating with NPM1 (55%; 241 of 436), and significantly higher than in other patients with AML who do not have NPM1 mutations or PML::RARA (22%; 235 of 1,039; P < 10–6, by χ2 test). This evidence concerns the gene FLT3 and acute myeloid leukemia.