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KRasG12D-evoked leukemogenesis does not require β-catenin

Leukemia volume 28, pages 698–702 (2014)Cite this article

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The targeting of self-renewal pathways commonly activated in leukemia serves as a potential strategy for multiple subtypes of this disease regardless of genetic, clonal or cellular heterogeneity. Elevation of β-catenin above physiological conditions enhances the self-renewal of normal hematopoietic stem cells (HSCs), and this attribute appears to be commonly utilized by leukemia cells.1 Dependency on elevated β-catenin activity in leukemia stem cells (LSCs) demonstrated in several different types of leukemia strongly suggests an essential and universal role for β-catenin in LSC function in leukemia.2, 3, 4, 5, 6 As normal adult HSCs do not require its basal activity,7 β-catenin has emerged as a potential LSC-specific therapeutic target.

Mutations in the Ras pathway are some of the most common in all human malignancies and occur across the spectrum of human blood neoplasms.8 These mutations usually in KRAS, NRAS or NF1 lead to stabilization of the GTP-bound active state of small Ras GTPases leading to over-activation of downstream Ras effector pathways.8 Endogenous levels of gain-of-function Ras proteins in mice lead to myeloproliferative neoplasms (MPNs) and/or T-cell acute lymphoblastic leukemia (T-ALL).9, 10, 11 Although this pathway has been intensely studied, direct pharmacological inhibition of mutant Ras proteins has proven to be extremely challenging.

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Acknowledgements

This work was supported in part by the National Cancer Institute (CA66996 and CA140575) and the Leukemia and Lymphoma Society. DK was supported by NIH NIDDK award K01DK092300.

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Author notes

  1. A Sinha, A Krivtsov, J Chang & S A Armstrong

    Present address: 2Current Address: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.,

  2. D Kalaitzidis

    Present address: 3Current Address: Department of Medicine, Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.,

Authors and Affiliations

  1. Division of Hematology/Oncology, Children’s Hospital Boston and Dana-Farber Cancer Institute, Harvard Medical School and the Harvard Stem Cell Institute, Boston, 02115, MA, USA

    C E L Ng, S Dias, S A Armstrong & D Kalaitzidis

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  1. C E L Ng
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Correspondence to S A Armstrong or D Kalaitzidis.

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Ng, C., Sinha, A., Krivtsov, A. et al. KRasG12D-evoked leukemogenesis does not require β-catenin. Leukemia 28, 698–702 (2014). https://doi.org/10.1038/leu.2013.328

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