Progress in Hematology Genetic and epigenetic alterations in hematopoietic malignancies

International Journal of Hematology

, Volume 97, Issue 2, pp 165-174

First online:

Gene mutations of acute myeloid leukemia in the genome era

  • Tomoki NaoeAffiliated withDepartment of Hematology and Oncology, Nagoya University Graduate School of Medicine Email author 
  • , Hitoshi KiyoiAffiliated withDepartment of Hematology and Oncology, Nagoya University Graduate School of Medicine


Ten years ago, gene mutations found in acute myeloid leukemia (AML) were conceptually grouped into class I mutation, which causes constitutive activation of intracellular signals that contribute to the growth and survival, and class II mutation, which blocks differentiation and/or enhance self-renewal by altered transcription factors. A cooperative model between two classes of mutations has been suggested by murine experiments and partly supported by epidemiological findings. In the last 5 years, comprehensive genomic analysis proceeded to find new gene mutations, which are found in the epigenome-associated enzymes and the molecules never noticed so far. These new mutations apparently increase the complexity and heterogeneity of AML. Although a long list of gene mutations might have been compiled, the entire picture of molecular pathogenesis in AML remains to be elucidated because gene rearrangement, gene copy number, DNA methylation and expression profiles are not fully studied in conjunction with gene mutations. Comprehensive genome research will deepen the understanding of AML to promote the development of new classification and treatment. This review focuses on gene mutations that were recently discovered by genome sequencing.


Acute myeloid leukemia Chromosome translocation Gene mutation Genome sequencing Epigenetics Prognosis