Drug resistance in mutant FLT3-positive AML

Oncogene. 2010 Sep 16;29(37):5120-34. doi: 10.1038/onc.2010.273. Epub 2010 Jul 12.


Mutant Fms-Like Tyrosine kinase-3 (FLT3), which is expressed in the leukemic cells of a subpopulation of acute myeloid leukemia (AML) patients, represents an attractive target for the therapy of AML. There are several FLT3 inhibitors presently in clinical trials with sufficient efficacy and toxicity features to warrant further testing in combination with standard therapies. However, the transient and partial responses observed in AML patients treated with FLT3 inhibitors, coupled with the discovery of drug-resistant leukemic blast cells in AML patients, have made resistance to FLT3 inhibitors a growing concern. In this study, we provide an overview of the role of mutant FLT3 in AML, FLT3 inhibitors under clinical and preclinical investigation, mechanisms of resistance to FLT3 inhibitors, and possible therapeutic approaches to overcoming this resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Drug Resistance, Neoplasm / genetics*
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics*
  • Mutation
  • Protein Kinase Inhibitors / therapeutic use*
  • Signal Transduction
  • fms-Like Tyrosine Kinase 3 / antagonists & inhibitors
  • fms-Like Tyrosine Kinase 3 / genetics*


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3