Genetic abnormalities in AML can be classified as disease-defining abnormalities that are mutually exclusive. So far, they encompass the 7 genetically defined WHO entities, 2 provisional WHO entities (NPM1 mutated, CEBPA double-mutated), and 2 suggested new WHO entities (MYST3-CREBBP, NUP98-NSD1). These are associated with a distinct cytomorphology and gene expression pattern. In addition, a specific pattern of HOXA and HOXB genes is recognized with MYST3-CREBBP being related to an elevated expression of HOXA, but not of HOXB genes. A further class comprises mutations that concomitantly occur and alter different cellular processes, such as signaling, chromatin modification, DNA methylation, RNA splicing, cohesion of sister chromatids, transcription, and tumor suppression.