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01-11-2019 | Essential Thrombocytosis | Original Article

Essential thrombocytosis attributed to JAK2-T875N germline mutation

Authors: Makoto Yoshimitsu, Miho Hachiman, Yuichiro Uchida, Naosuke Arima, Akihiko Arai, Yuhei Kamada, Kotaro Shide, Masafumi Ito, Kazuya Shimoda, Kenji Ishitsuka

Published in: International Journal of Hematology | Issue 5/2019

Abstract

The aim of this study was to elucidate the role of a non-canonical JAK2 mutation JAK2-T875N, which was identified by exome sequencing in a patient with essential thrombocytosis (ET) who had a family history of suspecting ET. Whole exome sequencing was performed on peripheral blood mononuclear cells and buccal swab-derived genomic DNA. Sanger sequencing was performed to confirm the variant. We evaluated the function of the mutation on JAK2 activity and downstream signaling (Erk, STATs) using JAK2-T875N-transfected or transduced cell lines. 293T cells transfected with JAK2 cDNA carrying V617F or T875N mutations showed increased levels of phosphorylated JAK2 and Erk. Enhanced STAT3 and STAT5 activity was confirmed by promoter assay. JAK2-T875N-transduced Ba/F3 cells showed increased cellular growth without IL-3 stimulation. To our knowledge, this is the first case of ET caused by JAK2-T875N mutation with a family history of thrombocytosis and cerebral infarction.

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Title: Essential thrombocytosis attributed to JAK2-T875N germline mutation
Authors: Makoto Yoshimitsu
Miho Hachiman
Yuichiro Uchida
Naosuke Arima
Akihiko Arai
Yuhei Kamada
Kotaro Shide
Masafumi Ito
Kazuya Shimoda
Kenji Ishitsuka
Publication date: 01-11-2019
Publisher: Springer Japan
Keywords: Essential Thrombocytosis
Ruxolitinib
Published in: International Journal of Hematology / Issue 5/2019
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-019-02725-8

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