The mechanisms of resistance to BRAF inhibitor therapy in HCL are associated with the acquisition of aberrations within the MEK/ERK signaling pathway (KRAS, MAP2K1 and IRS1 activating mutations or NF1 and NF2 deletions) that reactivate the pathway despite BRAF blockade [34,139,147]. The gene discussed is MAP2K7; the disease is hairy cell leukemia.