New avenues for genetics guided therapeutic approaches in AML

Abstract

The development of single nucleotide polymorphism (SNP) microarray analysis and next generation sequencing (NGS) has significantly contributed to comprehensively characterize the genetic changes underlying acute myeloid leukemia (AML). These genomics technologies have led to the identification of an increasing number of genomic aberrations and gene mutations that cause epigenetic changes and lead to deregulated gene expression. In accordance, AML patients present with a distinct and almost individual combination of somatically acquired genetic alterations reflecting the molecular heterogeneity of the disease. Some of these are known driver mutations perturbing self-renewal, proliferation, and hematopoietic differentiation, whereas many mutations also represent mere passenger events, which do not significantly contribute to AML. In the future, we will have to discriminate driver from passenger mutations and in addition it will be crucial to evaluate the prognostic and predictive values of the respective driver mutations, especially in the context of the overall genetic background. While first genetic markers have already been translated into the daily clinical routine by impacting treatment decisions, novel biomarkers are needed especially to improve the effectiveness of molecular targeted therapies, which have to be put into the perspective of mutational networks to further “precision medicine” by personalized combination treatment approaches.