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Ref Type Journal Article
PMID (30341394)
Authors Caeser R, Collord G, Yao WQ, Chen Z, Vassiliou GS, Beer PA, Du MQ, Scott MA, Follows GA, Hodson DJ
Title Targeting MEK in vemurafenib-resistant hairy cell leukemia.
Journal Leukemia
Vol
Issue
Date 2018 Oct 19
URL
Abstract Text

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
MAP2K1 F53C missense gain of function - predicted MAP2K1 F53C does not lie within any known functional domains of the Map2k1 protein (UniProt.org). F53C results in increased Erk1/2 phosphorylation in vitro and has been associated with resistance to BRAF inhibitors (PMID: 30341394), and therefore, is predicted to result in a gain of Map2k1 protein function. Y
MAP2K1 K57T missense gain of function - predicted MAP2K1 K57T lies within the negative regulatory region of the Map2k1 protein (PMID: 24241536). K57T results in increased Erk1/2 phosphorylation in culture (PMID: 30341394), and has been demonstrated to occur as a secondary drug resistance mutation (PMID: 26644315, PMID: 28819429, PMID: 30341394), and therefore, is predicted to result in a gain of Map2k1 protein function. Y
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600E MAP2K1 K57T refractory hairy cell leukemia predicted - sensitive Cobimetinib + Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a single patient with hairy cell leukemia who relapsed after initial response to Zelboraf (vemurafenib) was found to have acquired multiple clones with Mek/Erk activating mutations, of which the MAP2K1 K57T clone became dominant, and demonstrated a sustained response greater than 12 months to combined Zelboraf (vemurafenib) and Cotellic (cobimetinib) treatment (PMID: 30341394). 30341394
BRAF V600E MAP2K1 K57T hairy cell leukemia predicted - resistant Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a single patient with hairy cell leukemia harboring BRAF V600E, who relapsed after a 38 week remission in response to Zelboraf (vemurafenib) treatment, was found to have acquired multiple clones with Mek/Erk activating mutations, of which the MAP2K1 K57T clone became dominant (PMID: 30341394). 30341394