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

Journal article


Azorsa, DO, Lee, DW, Wai, DH, Bista, R, Patel, AR, Aleem, E, Henry, MM and Arceci, RJ (2018). Clinical resistance associated with a novel MAP2K1 mutation in a patient with Langerhans cell histiocytosis. Pediatric Blood and Cancer. 65 (9), pp. e27237-e27237.
AuthorsAzorsa, DO, Lee, DW, Wai, DH, Bista, R, Patel, AR, Aleem, E, Henry, MM and Arceci, RJ
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.

Year2018
JournalPediatric Blood and Cancer
Journal citation65 (9), pp. e27237-e27237
ISSN1545-5009
Digital Object Identifier (DOI)doi:10.1002/pbc.27237
Publication dates
Print16 May 2018
Publication process dates
Deposited12 Dec 2018
Accepted17 Apr 2018
Accepted author manuscript
License
CC BY-NC 4.0
Permalink -

https://openresearch.lsbu.ac.uk/item/86qxv

  • 5
    total views
  • 26
    total downloads
  • 0
    views this month
  • 1
    downloads this month

Related outputs

Nuclear insulin-like growth factor 1 receptor phosphorylates proliferating cell nuclear antigen and rescues stalled replication forks after DNA damage
Waraky, A, Lin, Y, Warsito, D, Haglund, F, Aleem, E and Larsson, O (2017). Nuclear insulin-like growth factor 1 receptor phosphorylates proliferating cell nuclear antigen and rescues stalled replication forks after DNA damage. Journal of Biological Chemistry. 292 (44), pp. 18227-18239.
Downregulation of IGF-1 receptor occurs after hepatic linage commitment during hepatocyte differentiation from human embryonic stem cells
Waraky, A, Aleem, E and Larsson, O (2016). Downregulation of IGF-1 receptor occurs after hepatic linage commitment during hepatocyte differentiation from human embryonic stem cells. Biochemical and Biophysical Research Communications. 478 (4), pp. 1575-1581.
Disulfiram overcomes bortezomib and cytarabine resistance in Down-syndrome-associated acute myeloid leukemia cells
Bista, R, Lee, DW, Pepper, OB, Azorsa, DO, Arceci, RJ and Aleem, E (2017). Disulfiram overcomes bortezomib and cytarabine resistance in Down-syndrome-associated acute myeloid leukemia cells. Journal of Experimental & Clinical Cancer Research. 36 (22).