Treatment of acute myeloid leukemia in the next decade - Towards real-time functional testing and personalized medicine

Blood Rev. 2017 Nov;31(6):418-425. doi: 10.1016/j.blre.2017.08.001. Epub 2017 Aug 4.

Abstract

Information arising from next generation sequencing of leukemia genome has shed important light on the heterogeneous and combinatorial driver events in acute myeloid leukemia (AML). It has also provided insight into its intricate signaling pathways operative in the disease pathogenesis. These have also become biomarkers and targets for therapeutic intervention. Emerging evidence from in vitro drug screening has demonstrated its potential value in predicting clinical drug responses in specific AML subtypes. However, the best culture conditions and readouts have yet to be standardized and the drugs included in these screening exercises frequently revised in view of the rapid emergence of new therapeutic agents in the oncology field. Testing of leukemia cell functions, including BCL2 profiling, has also been used to predict treatment response to conventional chemotherapy and hypomethylating agents as well as BCL2 antagonist in small patient cohorts. These platforms should be integrated into future clinical trials to develop personalized treatment of AML.

Keywords: Acute myeloid leukemia; BCL2 profiling; In-vitro drug screening; Next generation sequencing; Personalized medicine.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Drug Screening Assays, Antitumor / methods
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism
  • Molecular Targeted Therapy / methods
  • Precision Medicine / methods*
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-bcl-2