Design, implementation and clinical utility of next generation sequencing in myeloid malignancies: acute myeloid leukaemia and myelodysplastic syndrome

Abstract

Next generation sequencing (NGS) based technology has contributed enormously to our understanding of the biology of myeloid malignancies including acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). Assessment of clinically important mutations by NGS is a powerful tool to define diagnosis, determine prognostic risk, monitor measurable residual disease and uncover predictive mutational markers/therapeutic targets, and is now a routine component in the workup and monitoring of haematological disorders. There are many technical challenges in the design, implementation, analysis and reporting of NGS based results, and expert interpretation is essential. It is vital to distinguish relevant somatic disease associated mutations from those that are known polymorphisms, rare germline variants and clonal haematopoiesis of indeterminate potential (CHIP) associated variants. This review highlights and addresses the technical and biological challenges that should be considered before the implementation of NGS based testing in diagnostic laboratories and seeks to outline the essential and expanding role NGS plays in myeloid malignancies. Broad aspects of NGS panel design and reporting including inherent technological, biological and economic considerations are covered, following which the utility of NGS based testing in AML and MDS are discussed. In current practice, patient care is now strongly shaped by the results of NGS assessment and is considered a vital piece of the puzzle for clinicians as they manage these complex haematological disorders.

Keywords: Next generation sequencing; acute myeloid leukaemia; myelodysplastic syndrome; targeted panels.