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Drug resistance in mutant FLT3-positive AML

Oncogene volume 29, pages 5120–5134 (2010)Cite this article

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Abstract

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.

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Acknowledgements

This work is supported in part by the National Institutes of Health Grants (CA134660-02, MS; and CA36167 and DK50654, JDG), and a Leukemia and Lymphoma Society SCOR grant (JDG).

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  1. Department of Medical Oncology/Hematologic Neoplasia, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    E Weisberg, M Sattler, A Ray & J D Griffin

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Weisberg, E., Sattler, M., Ray, A. et al. Drug resistance in mutant FLT3-positive AML. Oncogene 29, 5120–5134 (2010). https://doi.org/10.1038/onc.2010.273

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