| Literature DB >> 31428969 |
Makoto Yoshimitsu1,2, Miho Hachiman3, Yuichiro Uchida3, Naosuke Arima4,3, Akihiko Arai4,3, Yuhei Kamada4, Kotaro Shide5, Masafumi Ito6, Kazuya Shimoda5, Kenji Ishitsuka4,3.
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.Entities:
Keywords: Essential thrombocythemia; Hereditary thrombocytosis; JAK2; JAK2-T875N; Myeloproliferative neoplasm
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Year: 2019 PMID： 31428969 DOI： 10.1007/s12185-019-02725-8
Source DB: PubMed Journal: Int J Hematol ISSN： 0925-5710 Impact factor: 2.490