The evolving molecular genetic landscape in acute myeloid leukaemia

Acute myeloid leukaemia (AML) is a heterogeneous disease with a variable response to therapy. The heterogeneity of AML is evident from variations in morphology, immunophenotype, cytogenetics and molecular abnormalities. The introduction of genome-wide technologies has enabled an even more detailed molecular analysis of AML. As a result, the molecular landscape of AML is rapidly evolving. The purpose of this review is to discuss the recent advances made in this field, with a special focus on risk stratification of AML.

Clinical AML has been analysed in great molecular detail by gene expression profiling and more recently through epigenetic profiling and next generation sequencing. This has resulted in the identification of novel biomarkers, some of which appear to have a consistent clinical impact in AML, that is mutations in the genes encoding DNA (cytosine-5)-methyltransferase 3 alpha (DNMT3A), additional sex combs-like 1 (ASXL1), tet methylcytosine dioxygenase 2 (TET2) and Runt-related transcription factor 1 (RUNX1). In addition, massively parallel sequencing has revealed a great mutational heterogeneity as well as temporal clonal evolution in AML.

The list of acquired mutations with clinical value in AML is growing. Clinical implementation of this multitude of markers will require integrated approaches and selection of markers to facilitate AML risk stratification in the future. The revealed molecular heterogeneity and evolution in AML will have implications for developing targeted therapies.