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Acute myeloid leukemia

Evaluation of ERK as a therapeutic target in acute myelogenous leukemia

Leukemia volume 34, pages 625–629 (2020)Cite this article

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A Correction to this article was published on 06 March 2020

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The mitogen-activated protein kinase (MAPK) signaling cascade, comprising key kinases including Raf, MEK1, and MEK2 (MAP2K1 and MAP2K2), and ERK1 and ERK2 (p44 MAPK and p42 MAPK), contributes to the growth, survival, and transformation of hematopoietic cells and is a promising target for acute myeloid leukemia (AML) therapy [1, 2]. RAS is a major target of activating mutations in AML and ERK is a key regulator of multiple signaling pathways.

Despite its prevalence in AML, targeting of mutant RAS directly has proven to be difficult because of its molecular configuration [3]. Attempts have been made to target Ras signaling through other, more indirect, approaches, such as inhibition of MEK, mTOR, ATK, PI3K, and Raf; however, clinical testing of these alternative strategies has been disappointing because of compensatory activation of other signaling molecules or negative feedback loops [4,5,6].

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Acknowledgements

This work was funded by Eli Lilly and Company, and the Project Program Grant, NIH PO1CA66996.

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  1. These authors contributed equally: Ellen Weisberg, Chengcheng Meng, Abigail Case

Authors and Affiliations

  1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Ellen Weisberg, Chengcheng Meng, Abigail Case, Martin Sattler, Richard Stone, Suiyang Liu, Sophia Adamia & James D. Griffin

  2. Department of Medicine, Harvard Medical School, Boston, MA, USA

    Ellen Weisberg, Martin Sattler, Richard Stone, Sophia Adamia & James D. Griffin

  3. Experimental Therapeutic Core, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA, 02215

    Hong L. Tiv & Prafulla C. Gokhale

  4. Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA, 02215

    Sara Buhrlage

  5. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA

    Jinhua Wang & Nathanael Gray

  6. Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 46285, USA

    Shripad V. Bhagwat & Ramon V. Tiu

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Correspondence to Ellen Weisberg or James D. Griffin.

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Conflict of interest

JDG receives funding and has received a royalty payment from Novartis Pharmaceuticals and receives funding from Eli Lilly and Company. N is a founder, science advisory board member (SAB), and equity holder in Gatekeeper, Syros, Petra, C4, B2S, and Soltego. The Gray lab receives or has received research funding from Novartis, Takeda, Astellas, Taiho, Janssen, Kinogen, Voronoi, Her2llc, Deerfield, and Sanofi. EW has received a royalty payment from Novartis Pharmaceuticals. RS does Ad Hoc consulting for and receives clinical research support to Dana-Farber Cancer Institute from the following companies: Abbvie, Agios, Arog, and Novartis. He does Ad Hoc consulting for the following companies: Astrazeneca, Cornerstone, Jazz, Daiichi-Sankyo, Otsuka/Astex, Pfizer, and Stemline. He is on the Advisory Board of the following companies: Actinium, Amgen, Astellas, and Macrogenics. He is on the Data Safety and Monitoring Board for the following companies: Argenx, Celgene, and Takeda. He is an Ad Hoc Consultant and on the Steering Committee and Data Safety and Monitoring Board for Celgene. SVB is an employee and shareholder of Eli Lilly and Company. RVT was an employee and is a shareholder of Eli Lilly and Company, and is currently employed by Astellas Pharma.

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Weisberg, E., Meng, C., Case, A. et al. Evaluation of ERK as a therapeutic target in acute myelogenous leukemia. Leukemia 34, 625–629 (2020). https://doi.org/10.1038/s41375-019-0552-3

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