NPM1 and acute myeloid leukemia: In combination with other class-defining mutations, such as t(15;17), t(8;21), inv(16), t(6;9), KMT2A fusion genes, complex karyotype, or driver mutations in NPM1, TP53, or CEBPA biallelic mutations, two or more of the CS-mutations are required to define CS-AML (Figure 1).