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Dasatinib promotes ATRA-induced differentiation of AML cells

Leukemia volume 24, pages 663–665 (2010)Cite this article

Dasatinib is a US Food and Drug Administration-approved compound that was developed as an inhibitor of ABL and Src family kinases (SFKs).1 Dasatinib is substantially more potent than imatinib against wild-type BCR–ABL. Moreover, with the exception of the T315I mutant, dasatinib retains activity against most imatinib-resistant BCR–ABL mutants, helping to explain the effectiveness of dasatinib in all stages of imatinib-resistant CML. The efficacy of dasatinib in CML is furthered by the ability of this compound to inhibit the SFK member LYN, which is persistently hyperactivated in imatinib-resistant disease.2

Recent studies have revealed dasatinib effects on hematopoietic cells other than CML, and have suggested additional therapeutic opportunities, as well as adverse toxicities. Dasatinib inhibits the production of osteoclasts and tumor-associated macrophages, as well as the functional activities of osteoclasts, platelets, T cells and natural killer cells.3, 4, 5, 6, 7 As these cell types do not express BCR–ABL, inhibition of SFK members such as LYN, or other kinase targets, is likely responsible for the effects of dasatinib on these cells.

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Acknowledgements

We thank Bristol-Myers Squibb (New York, NY) for providing dasatinib. This work was supported by National Institutes of Health Grant R01 CA108904.

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Authors and Affiliations

  1. Department of Medicine, University of Pittsburgh and the University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA

    P L Kropf, L Wang, Y Zang, R L Redner & D E Johnson

  2. Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA, USA

    D E Johnson

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Correspondence to D E Johnson.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Kropf, P., Wang, L., Zang, Y. et al. Dasatinib promotes ATRA-induced differentiation of AML cells. Leukemia 24, 663–665 (2010). https://doi.org/10.1038/leu.2009.267

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