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Acute myeloid leukemia (AML) is a genetically heterogeneous disease for which the treatment armamentarium has been historically restricted to chemotherapy. However, genomic and epigenomic alterations that contribute to AML initiation, maintenance, and relapse have disclosed new insights to the 5th update in WHO Classification of Haematolymphoid Tumours. After four decades of intensive chemotherapy as a ‘one-size-fits-all’ concept, several targeted agents have been approved for the treatment of AML. Several compounds, directed against regulators of apoptotic, epigenetic, or micro-environmental pathways, and immune-system modulators, are currently in development and investigation in clinical trials. We review advances in target-based therapy for AML focusing on their mechanism of action, examining the intracellular events and pathways, and the results from published clinical trials. To improve patient clinical outcomes, find new biomarkers for therapeutic response, and pinpoint patients who might benefit from novel targeted medicines, next-generation sequencing is being used to evaluate AML-associated mutations. In fact, the new 5th edition of WHO classification has reaffirmed the importance of genetically defined entities that have a prognostic impact, but not all have a specific treatment available. New class of target drugs are in clinical development and could be beneficial to improve the therapeutic armamentarium available.

Molecular targets for the treatment of AML in the forthcoming 5th World Health Organization Classification of Haematolymphoid Tumours