Genomic landscape in acute myeloid leukemia and its implications in risk classification and targeted therapies

Abstract

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy in terms of clinical features, underlying pathogenesis and treatment outcomes. Recent advances in genomic techniques have unraveled the molecular complexity of AML leukemogenesis, which in turn have led to refinement of risk stratification and personalized therapeutic strategies for patients with AML. Incorporation of prognostic and druggable genetic biomarkers into clinical practice to guide patient-specific treatment is going to be the mainstay in AML therapeutics. Since 2017 there has been an explosion of novel treatment options to tailor personalized therapy for AML patients. In the past 3 years, the U.S. Food and Drug Administration approved a total of eight drugs for the treatment of AML; most specifically target certain gene mutations, biological pathways, or surface antigen. These novel agents are especially beneficial for older patients or those with comorbidities, in whom the treatment choice is limited and the clinical outcome is very poor. How to balance efficacy and toxicity to further improve patient outcome is clinically relevant. In this review article, we give an overview of the most relevant genetic markers in AML with special focus on the therapeutic implications of these aberrations.

Keywords: Acute myeloid leukemia; Genetic markers; Risk stratification; Therapeutics.

Fig. 1

Common molecular gene mutations and their incidences in 763 AML patients in Taiwan. The data are derived from the mutation analyses of 763 patients diagnosed and treated at the National Taiwan University Hospital

Fig. 2

The Circos plots depicting the relative frequency and pairwise co-occurrence of genetic alterations in 500 AML patients in Taiwan. The length of the arc corresponds to the frequency of the first gene mutation, and the width of the ribbon corresponds to the proportion of the second gene mutation. The data are derived from the mutation analyses of 500 patients diagnosed and treated at the National Taiwan University Hospital

Fig. 3

Survival curves of 763 AML patients in Taiwan stratified according to the 2017 ELN risk stratification. The data are derived from the mutation analyses of 763 patients diagnosed and treated at the National Taiwan University Hospital