Molecular Genetic Markers in Acute Myeloid Leukemia.

Sophia Yohe

doi:10.3390/jcm4030460

Abstract

Genetics play an increasingly important role in the risk stratification and management of acute myeloid leukemia (AML) patients. Traditionally, AML classification and risk stratification relied on cytogenetic studies; however, molecular detection of gene mutations is playing an increasingly important role in classification, risk stratification, and management of AML. Molecular testing does not take the place of cytogenetic testing results, but plays a complementary role to help refine prognosis, especially within specific AML subgroups. With the exception of acute promyelocytic leukemia, AML therapy is not targeted but the intensity of therapy is driven by the prognostic subgroup. Many prognostic scoring systems classify patients into favorable, poor, or intermediate prognostic subgroups based on clinical and genetic features. Current standard of care combines cytogenetic results with targeted testing for mutations in FLT3, NPM1, CEBPA, and KIT to determine the prognostic subgroup. Other gene mutations have also been demonstrated to predict prognosis and may play a role in future risk stratification, although some of these have not been confirmed in multiple studies or established as standard of care. This paper will review the contribution of cytogenetic results to prognosis in AML and then will focus on molecular mutations that have a prognostic or possible therapeutic impact.

Highlights

There is a well-established role for genetic classification of acute myeloid leukemia (AML) into different prognostic groups
This paper will briefly review the contribution of cytogenetic results to prognosis in AML and will focus on molecular mutations that change prognostic subgrouping
Isolated NPM1 or biallelic CEBPA mutations improve the prognosis of AML with normal cytogenetics from intermediate to favorable; whereas a FLT3 internal tandem duplication (ITD) changes it to poor

Summary

Introduction

There is a well-established role for genetic classification of acute myeloid leukemia (AML) into different prognostic groups This classification has relied on detection of large chromosomal abnormalities by cytogenetics; detection of smaller scale mutations is playing an increasingly important role in classification and prognostication of AML. These mutations do not take the place of cytogenetic testing results but play a complementary role to help refine prognosis, especially within specific AML subgroups. Research on molecular testing has generally tried to refine the prognosis of intermediate cases or to find mutations that explain why some patients in a favorable prognosis category have resistant disease. Gene mutations that appear to have prognostic effect but have not been confirmed in multiple studies or established as standard of care will be explored

Genetics and AML Classification

Cytogenetic Abnormalities and Prognosis

Established Gene Mutations Associated with Prognosis

Other Gene Mutations in AML

Findings

Conclusions