Molecular Landscape of Acute Myeloid Leukemia: Prognostic and Therapeutic Implications

Abstract

Purpose of review: The field of acute myeloid leukemia (AML) has been revolutionized in recent years by the advent of high-throughput techniques, such as next-generation sequencing. In this review, we will discuss some of the recently identified mutations that have defined a new molecular landscape in this disease, as well as their prognostic, predictive, and therapeutic implications.

Recent findings: Recent studies have shown how many cases of AML evolve from a premalignant period of latency characterized by the accumulation of several mutations and the emergence of one or multiple dominant clones. The pattern of co-occurring mutations and cytogenetic abnormalities at diagnosis defines risk and can determine therapeutic approaches to induce remission. Besides the genetic landscape at diagnosis, the continued presence of particular gene mutations during or after treatment carries prognostic information that should further influence strategies to maintain remission in the long term. The recent progress made in AML research is a seminal example of how basic science can translate into improving clinical practice. Our ability to characterize the genomic landscape of individual patients has not only improved our ability to diagnose and prognosticate but is also bringing the promise of precision medicine to fruition in the field.

Keywords: Clonal evolution; Genomics; Mutations; Preleukemia; Prognosis; Targeted therapy.

Fig. 1

Timing of the identification of mutations associated with AML and evolution of therapeutic strategies. More widespread use of sequencing technologies has enriched the landscape of mutations that are associated with AML. An enhanced ability to diagnose and prognosticate is now translating into an increased understanding of therapeutic vulnerabilities and the development of new therapies. Between 2017 and 2018, the FDA has approved eight novel drugs for the treatment of AML and for the first time in almost 40 years, and AML patients can benefit from a more individualized treatment approach