Genetic biomarkers in acute myeloid leukemia: will the promise of improving treatment outcomes be realized?

Expert Rev Hematol. 2012 Aug;5(4):395-407. doi: 10.1586/ehm.12.32.

Abstract

Recent progress in the molecular genetics of acute myeloid leukemia (AML) has shown this disease to be more heterogeneous than previously realized. Recurrent cytogenetic and mutational changes in leukemic blasts have been confirmed to have high prognostic significance. High-throughput techniques to analyze the AML genome in greater depth have revealed novel mutations with putative roles in leukemogenesis. The use of prognostic biomarkers has allowed for a more detailed categorization of AML based on risk. Despite this tremendous progress, the understanding of the mechanisms by which these changes influence leukemia growth and response to treatment is still limited, which in turn has hindered the development of rationally targeted therapies for AML. The integration of clinical, cytogenetic and molecular data will be essential to translate the current research momentum into better outcomes for patients with AML.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Biomarkers / metabolism*
  • CCAAT-Enhancer-Binding Proteins / genetics
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methyltransferase 3A
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dioxygenases
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Isocitrate Dehydrogenase / metabolism
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nucleophosmin
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • Risk Factors
  • fms-Like Tyrosine Kinase 3 / genetics
  • fms-Like Tyrosine Kinase 3 / metabolism

Substances

  • Antineoplastic Agents
  • Biomarkers
  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, human
  • DNA-Binding Proteins
  • DNMT3A protein, human
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Nucleophosmin
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • Dioxygenases
  • TET2 protein, human
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3