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  • Review Article
  • Published:

Molecular therapy for acute myeloid leukaemia

Nature Reviews Clinical Oncology volume 13, pages 305–318 (2016)Cite this article

Subjects

Key Points

  • More than 97% of patients with acute myeloid leukaemia (AML) demonstrate at least one clonal somatic abnormality on comprehensive mutational profiling, which is increasingly being performed in the clinic

  • Unique mutational profiles can be used to predict a response to both standard and investigational therapies in patients with newly diagnosed or relapsed and/or refractory AML

  • Molecular abnormalities associated with AML are also predictors of outcome following allogeneic haematopoietic-stem-cell transplantation

  • Comprehensive mutational profiling should be performed in all newly diagnosed patients with AML using standardized high-throughput assays

  • Comprehensive mutational profiling will enable consideration of novel targeted agents in the upfront setting, either alone or in combination with chemotherapy, and we hypothesize that this approach will improve outcomes of patients with this disease

Abstract

Acute myeloid leukaemia (AML) is a heterogeneous disease that is, in general, associated with a very poor prognosis. Multiple cytogenetic and molecular abnormalities that characterize different forms of AML have been used to better prognosticate patients and inform treatment decisions. Indeed, risk status in patients with this disease has classically been based on cytogenetic findings; however, additional molecular characteristics have been shown to inform risk assessment, including FLT3, NPM1, KIT, and CEBPA mutation status. Advances in sequencing technology have led to the discovery of novel somatic mutations in tissue samples from patients with AML, providing deeper insight into the mutational landscape of the disease. The majority of patients with AML (>97%) are found to have a clonal somatic abnormality on mutational profiling. Nevertheless, our understanding of the utility of mutation profiling in clinical practice remains incomplete and is continually evolving, and evidence-based approaches to application of these data are needed. In this Review, we discuss the evidence-base for integrating mutational data into treatment decisions for patients with AML, and propose novel therapeutic algorithms in the era of molecular medicine.

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Figure 1: Proposed treatment algorithm for patients aged >60 years with newly diagnosed AML.
Figure 2: Proposed treatment algorithm for patients aged ≤60 years with newly diagnosed AML.

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Authors and Affiliations

  1. Department of Medicine, Leukemia Service, Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, 10065, New York, USA

    Catherine C. Coombs, Martin S. Tallman & Ross L. Levine

  2. Weill Cornell Medical Center, 1300 York Avenue, New York, 10065, New York, USA

    Martin S. Tallman

  3. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, 10065, New York, USA

    Ross L. Levine

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  1. Catherine C. Coombs
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All of the authors made substantial contributions to researching data for article, discussion of content, and review/editing of manuscript before submission. C.C.C. wrote the manuscript.

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Coombs, C., Tallman, M. & Levine, R. Molecular therapy for acute myeloid leukaemia. Nat Rev Clin Oncol 13, 305–318 (2016). https://doi.org/10.1038/nrclinonc.2015.210

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