Essential thrombocytosis attributed to JAK2-T875N germline mutation
| Autor: | Kenji Ishitsuka, Yuichiro Uchida, Makoto Yoshimitsu, Kazuya Shimoda, Miho Hachiman, Masafumi Ito, Yuhei Kamada, Naosuke Arima, Kotaro Shide, Akihiko Arai |
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| Rok vydání: | 2019 |
| Předmět: |
STAT3 Transcription Factor
medicine.medical_specialty Biology medicine.disease_cause Transfection Peripheral blood mononuclear cell symbols.namesake Germline mutation hemic and lymphatic diseases Internal medicine medicine STAT5 Transcription Factor Humans Phosphorylation Medical History Taking Exome sequencing Germ-Line Mutation Sanger sequencing Mutation Hematology Thrombocytosis food and beverages Sequence Analysis DNA Janus Kinase 2 medicine.disease Molecular biology HEK293 Cells symbols hormones hormone substitutes and hormone antagonists Thrombocythemia Essential |
| Zdroj: | International journal of hematology. 110(5) |
| ISSN: | 1865-3774 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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