International Journal of Hematology

DOI: 10.1007/s12185-019-02725-8 Pages: 1-7

Essential thrombocytosis attributed to JAK2-T875N germline mutation

1. Kagoshima University Hospital, Department of Hematology and Rheumatology

2. Kagoshima University, Division of Hematology and Rheumatology, Graduate School of Medical and Dental Sciences

3. University of Miyazaki, Department of Gastroenterology and Hematology, Faculty of Medicine

4. Japanese Red Cross Nagoya First Hospital, Department of Pathology

Correspondence to:
Makoto Yoshimitsu
Tel: +81-099-275-5934
Email: myoshimi@m.kufm.kagoshima-u.ac.jp

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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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