Alternative genetic mechanisms of BRAF activation in Langerhans cell histiocytosis

Authors: Rikhia Chakraborty, Thomas M. Burke, Oliver Hampton, Daniel Zinn, Karen Phaik Har Lim, Harshal Abhyankar, Brooks Scull, Vijetha Kumar, Nipun Kakkar, David A. Wheeler, Angshumoy Roy, Poulikos I. Poulikakos, Miriam Mérad, Kenneth L. McClain, D. Williams Parsons, Carl E. Allen - Blood 2016 cited by 169

cells from lesions. ERK activation was resistant to BRAF-V600E inhibition, but responsive to both a second-generation BRAF inhibitor and a MEK inhibitor. These results support an emerging model of universal ERK-activating genetic alterations driving pathogenesis in LCH. A personalized approach in which patient-specific alterations are identified may be necessary to maximize benefit from targeted therapies for patients with LCH.