What do functional genomics tell us about pathogenesis of AML?

Best Pract Res Clin Haematol. 2019 Dec;32(4):101101. doi: 10.1016/j.beha.2019.101101. Epub 2019 Oct 18.

Abstract

While molecular genetic abnormalities can tell us much about the pathogenesis of acute myeloid leukemia (AML), these molecular genetics do not always explain drug resistance or sensitivity, leaving room for other mechanisms of tumor pathogenesis outside of genetic events. The Beat AML 1.0 project was a multicenter project to sequence and functionally query AML samples against over 120 drugs. The results have helped form disease models on how mutations affect disease phenotype and drug sensitivity and have assisted in identifying gene signature profiles that may facilitate selecting the most effective treatment options. However, there are factors outside of genetic abnormalities that affect disease pathogenesis. For example, tumor-associated macrophages in the tumor microenvironment play a role in pathogenesis and represent therapeutic targets.

Keywords: AML; Acute myeloid leukemia; Beat AML 1.0; Microenvironment; Pathogenesis; Tumor-associated macrophage.

Publication types

  • Review

MeSH terms

  • Gene Expression Profiling*
  • Gene Expression Regulation, Leukemic*
  • Genomics*
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / physiopathology
  • Mutation*