Clinical resistance associated with a novel MAP2K1 mutation in a patient with Langerhans cell histiocytosis
AuthorAzorsa, David O
Lee, David W
Wai, Daniel H
Patel, Apurvi R
Henry, Michael M
Arceci, Robert J
AffiliationUniversity of Arizona College of Medicine - Phoenix
MetadataShow full item record
CitationAzorsa, D. O., Lee, D. W., Wai, D. H., Bista, R., Patel, A. R., Aleem, E., ... & Arceci, R. J. (2018). Clinical resistance associated with a novel MAP2K1 mutation in a patient with Langerhans cell histiocytosis. Pediatric blood & cancer, 65(9), e27237.
JournalPediatric Blood & Cancer
Rights©2018 Wiley Periodicals, Inc.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractPatients with Langerhans cell histiocytosis (LCH) harbor BRAF V600E and activating mutations of MAP2K1/MEK1 in 50% and 25% of cases, respectively. We evaluated a patient with treatment-refractory LCH for mutations in the RAS-RAF-MEK-ERK pathway and identified a novel mutation in the MAP2K1 gene resulting in a p.L98_K104 > Q deletion and predicted to be auto-activating. During treatment with the MEK inhibitor trametinib, the patient's disease showed significant progression. In vitro characterization of the MAP2K1 p.L98_K104 > Q deletion confirmed its effect on cellular activation of the ERK pathway and drug resistance.
Note12 month embargo; first published: 16 May 2018
VersionFinal accepted manuscript
SponsorsSharon D. Lund Foundation; University of Arizona COM-P Department of Child Health Mission Support; Phoenix Children's Hospital Foundation
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