| RRC ID |
58014
|
| 著者 |
Yoshimitsu M, Hachiman M, Uchida Y, Arima N, Arai A, Kamada Y, Shide K, Ito M, Shimoda K, Ishitsuka K.
|
| タイトル |
Essential thrombocytosis attributed to JAK2-T875N germline mutation.
|
| ジャーナル |
Int J Hematol
|
| 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.
|
| 巻・号 |
110(5)
|
| ページ |
584-590
|
| 公開日 |
2019-11-1
|
| DOI |
10.1007/s12185-019-02725-8
|
| PII |
10.1007/s12185-019-02725-8
|
| PMID |
31428969
|
| MeSH |
Germ-Line Mutation / physiology*
HEK293 Cells
Humans
Janus Kinase 2 / genetics*
Janus Kinase 2 / metabolism
Medical History Taking
Phosphorylation
STAT3 Transcription Factor / metabolism
STAT5 Transcription Factor / metabolism
Sequence Analysis, DNA
Thrombocythemia, Essential / genetics*
Transfection
|
| IF |
2.245
|
| 引用数 |
0
|
| リソース情報 |
| ヒト・動物細胞 |
Ba/F3-CL1(RCB4474) |
