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

David O. Azorsa; David W. Lee; Daniel H. Wai; Ranjan Bista; Apurvi R. Patel; Eiman Aleem; Michael M. Henry; Robert J. Arceci

doi:10.1002/pbc.27237

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

David O. Azorsa, David W. Lee, Daniel H. Wai, Ranjan Bista, Apurvi R. Patel, Eiman Aleem, Michael M. Henry, Robert J. Arceci

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

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.

Original language	English
Article number	e27237
Pages (from-to)	e27237-e27237
Journal	Pediatric Blood and Cancer
Volume	65
Issue number	9
DOIs	https://doi.org/10.1002/pbc.27237 https://doi.org/10.1002/pbc.27237
Publication status	Published - 16 May 2018
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2018 Wiley Periodicals, Inc.

Keywords

Langerhans cell histiocytosis
MAP2K1
mutation

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10.1002/pbc.27237
10.1002/pbc.27237Licence: CC BY-NC 4.0

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title = "Clinical resistance associated with a novel MAP2K1 mutation in a patient with Langerhans cell histiocytosis",

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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doi = "10.1002/pbc.27237",

language = "English",

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AU - Azorsa, David O.

AU - Lee, David W.

AU - Wai, Daniel H.

AU - Bista, Ranjan

AU - Patel, Apurvi R.

AU - Aleem, Eiman

AU - Henry, Michael M.

AU - Arceci, Robert J.

PY - 2018/5/16

Y1 - 2018/5/16

N2 - 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.

AB - 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.

KW - Langerhans cell histiocytosis

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KW - mutation

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DO - 10.1002/pbc.27237

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

Abstract

Bibliographical note

Keywords

UN SDGs

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