Acute myeloid leukemia – molecular diagnostics in 2021

Acute myeloid leukemia (AML) develops as a clonal expansion of undifferentiated myeloid precursors that have somatically acquired mutations, which account for the biological and clinical complexity of the disease. Over the past decades, there has been a growing knowledge on the pathogenic relevance of these genomic aberrations. Recently, molecular genomic diagnostics have begun to be translated into the clinic, and mechanisms of clonal leukemia evolution and disease dynamics are starting to be understood, especially as novel next generation sequencing (NGS) technologies allow us to capture multiple competing clones coexisting at any disease time point. This review provides a short summary of molecular diagnostics and the impact of genomic changes on the individual patient outcome. Molecular diagnostics forms the basis for novel genomic classification schemes that are reproducible and clinically relevant. In accordance, next to the well-established molecular markers NPM1, CEBPA, and FLT3, the updated version of the European LeukemiaNet (ELN) guidelines also recommends the screening for RUNX1, TP53, and ASXL1 mutations. In the future, these as well as other AML associated aberrations will not only be crucial in determining measurable residual disease (MRD), but also in guiding targeted therapeutic approaches and novel genome-wide approaches will lead the way.