NPM1 and acute myeloid leukemia: The complexity of mutation co-occurrence is such that the negative prognostic impact of FLT3-ITD may be most relevant to AML with the most frequent three-gene co-occurrence of mutations in NPM1, DNMT3A, and FLT-3 whereas, the negative impact on survival in AML with FLT3-ITD and NPM1 mutation or FLT3-ITD and DNMT3A mutation is less pronounced irrespective of the FLT3-ITD allelic frequency (12).