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

Hsin-An Hou,Hwei-Fang Tien

doi:10.1186/s12929-020-00674-7

Hsin-An Hou, Hwei-Fang Tien

Open Access

https://doi.org/10.1186/s12929-020-00674-7

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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.

Highlights

Acute myeloid leukemia (AML) is a clonal hematologic malignancy with great variability in the clinical features, pathogenesis and treatment outcomes [1, 2]
The findings offer a potentially attractive therapeutic approach in AML with Enhancer of Zest Homologue 2 gene (EZH2) mutations and the EZH2 inhibitor is currently under development or early phase trials
Midostaurin (PKC412) is the first FMS-like tyrosine kinase 3 gene (FLT3) inhibitor approved by the U.S as well as Taiwan Food and Drug Administration (FDA) for the treatment of newly-diagnosed FLT3-mutated AML patients based on its effect on improving overall survival (OS) when combined with traditional chemotherapy [112, 113]

Summary

Introduction

Acute myeloid leukemia (AML) is a clonal hematologic malignancy with great variability in the clinical features, pathogenesis and treatment outcomes [1, 2]. Somatic mutations in genes regulating epigenetic modifications, such as IDH, TET2, DNMT3A, ASXL1, EZH2 and KMT2A are frequently detected in patients with AML, especially those with intermediate-risk cytogenetics [19, 76,77,78,79,80]. Midostaurin (PKC412) is the first FLT3 inhibitor approved by the U.S as well as Taiwan FDA for the treatment of newly-diagnosed FLT3-mutated AML patients based on its effect on improving OS when combined with traditional chemotherapy [112, 113].

Results

Conclusion