Impact of genomics in the clinical management of patients with cytogenetically normal acute myeloid leukemia

Best Pract Res Clin Haematol. 2015 Jun-Sep;28(2-3):90-7. doi: 10.1016/j.beha.2015.10.005. Epub 2015 Oct 22.

Abstract

Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous disease. Cytogenetics and FISH have contributed to the stratification of AML patients into favorable, intermediate, and unfavorable risk categories. However, until recently, the prognostic stratification and treatment decision for the intermediate risk category, mostly comprising AML patients with normal cytogenetics (CN-AML), has been difficult due to the scarce knowledge of the molecular alterations underlying this large AML subgroup (which accounts for about 50% of all adult AML). During the past decade, the discovery of numerous mutations associated with CN-AML has resulted in significant advances in the AML field. Here, we review the biological characteristics of the most common mutations underlying CN-AML and outline their clinical impact in the following settings: (i) definition of new molecular leukemia entities in the WHO classification; (ii) risk stratification of CN-AML patients according to mutational profile; and (iii) monitoring of minimal residual disease by specific quantitative molecular assays.

Keywords: Acute meyloid leukemia (AML); Genetics; Minimal residual disease (MRD); Mutations; Nucleophosmin (NPM1).

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Cytogenetic Analysis
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methyltransferase 3A
  • Gene Expression
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Mutation*
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Neoplasm, Residual
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Nucleophosmin
  • Patient Selection
  • Prognosis
  • Risk
  • Terminology as Topic
  • fms-Like Tyrosine Kinase 3 / genetics*
  • fms-Like Tyrosine Kinase 3 / metabolism

Substances

  • Antineoplastic Agents
  • DNMT3A protein, human
  • NPM1 protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • Nucleophosmin
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3