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Rac guanosine triphosphatases represent a potential target in AML

Leukemia volume 22, pages 1803–1806 (2008)Cite this article

In summary, we demonstrate the impact of Rac inhibition on a panel of human AML cell lines. Whereas the drug target GTP-Rac was present in all cell lines (not shown), the MLL gene-rearranged cell line ML-2 displayed the most profound dependence on Rac signaling. This finding is consistent with recently published findings in human CD34+ cells transduced with the MLL-AF9 oncogene and corroborated by our findings in the MLL-AF9-positive THP-1 cell line.5 The effect of NSC23766 may point to a potential specific vulnerability of MLL rearranged leukemia to Rac inhibition. The mechanism by which the other cell lines bypass this pathway will require further studies. Taken together, our findings highlight the Rac GTPases as potential molecular targets for a subgroup of AML. Development of more potent inhibitors of Rac GTPases is warranted to enable clinical use of this approach.

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Acknowledgements

This study was supported by National Institute of Health Grant numbers HL69974 and DK62757 (DAW), St Baldrick's Foundation Fellowship (LM) and CancerFree Kids grant (RJS). The authors thank James Mulloy, Junping Wei and Michael Milsom for critical review of the manuscript and the Division of Experimental Hematology Translational Trials Development and Support Laboratory for providing normal donor human CD34+ cells.

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Author notes

  1. R J Schore

    Present address: 4Current address: Leukemia and Lymphoma Program, Division of Oncology, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC, USA.,

  2. Y Gu

    Present address: 5Current address: Innovation Center China, AstraZeneca, Shanghai 201203, China.,

  3. L U W Müller and R J Schore: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Experimental Hematology, Cincinnati Children's Research Foundation, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, OH, USA

    L U W Müller, R J Schore, Y Zheng, E K Thomas, J A Cancelas, Y Gu & D A Williams

  2. Cincinnati Children's Research Foundation, Center for Epidemiology and Biostatistics, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, OH, USA

    M-O Kim

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  1. L U W Müller
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  6. J A Cancelas
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Correspondence to D A Williams.

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

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Müller, L., Schore, R., Zheng, Y. et al. Rac guanosine triphosphatases represent a potential target in AML. Leukemia 22, 1803–1806 (2008). https://doi.org/10.1038/leu.2008.196

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