Genetic profiling in acute myeloid leukaemia ─ where are we and what is its role in patient management

Summary Genetic profiling in acute myeloid leukaemia ( AML ) is a moving target. Only 4 years ago, AML was re‐classified, based on karyotypic abnormalities. However, numerous important new mutations and other genetic abnormalities that were not considered in this classification have been identified. Current cytogenetic‐based classification is limited by the substantial number of intermediate‐risk patients in whom the preferred therapy is debatable. In addition, the majority of AML patients co‐express multiple mutations and cannot be easily categorized into predefined homogenous groups. The tremendous progress in mass sequencing allows parallel identification of multiple genetic aberrations in large cohorts. Thus, a new concept of genetic profiling has arisen. Genes and proteins biologically interact with each other; therefore, it should not be surprising that mutations in different genes interact. Prognosis is determined by the composition of mutations and aberrations in leukaemic stem cells. As a consequence, clinical decisions no longer rely on scant genetic data and require comprehensive genetic evaluation. Some non‐genetic parameters are also important and should be incorporated into the clinical decision algorithm. Genetic interaction‐based profiles are challenging and recent studies demonstrate an improvement in prognostic predictions with this model. Thus, genetic profiling is likely to have a major therapeutic impact, at least for intermediate‐risk cytogenetics.