Clinical resistance associated with a novel MAP2K1 mutation in a patient with Langerhans cell histiocytosis

Pediatric Blood & Cancer
David O AzorsaRobert J Arceci

Abstract

Patients 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.

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Citations

Jul 13, 2020·International Journal of Hematology·Tomomi HayaseAkira Morimoto
Oct 2, 2021·Journal of Cancer Research and Clinical Oncology·Ying YangTianyou Wang

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