Cooperative Epigenetic Remodeling by TET2 Loss and NRAS Mutation Drives Myeloid Transformation and MEK Inhibitor Sensitivity

Cancer Cell

First published:  December 21, 2017

DOI: https://doi.org/10.1016/j.ccell.2017.11.012

Hiroyoshi Kunimoto, Cem Meydan, Abbas Nazir, Justin Whitfield, Kaitlyn Shank, Franck Rapaport, Rebecca Maher, Elodie Pronier, Sara C. Meyer, Francine E. Garrett-Bakelman, Martin Tallman, Ari Melnick, Ross L. Levine13, Alan H. 

Background: Mutations in epigenetic modifiers and signaling factors often co-occur in myeloid malignancies, including TET2 and NRAS mutations. Concurrent Tet2 loss and Nras^G12D expression in hematopoietic cells induced myeloid transformation, with a fully penetrant, lethal chronic myelomonocytic leukemia (CMML), which was serially transplantable. 

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