JAK2S523L, a novel gain-of-function mutation in a critical autoregulatory residue in JAK2V617F(-) MPNs Journal Article
| Authors: | Pastore, F.; Krishnan, A.; Hammaren, H. M.; Silvennoinen, O.; Yan, B.; Levine, R. L. |
| Article Title: | JAK2S523L, a novel gain-of-function mutation in a critical autoregulatory residue in JAK2V617F(-) MPNs |
| Abstract: | The SH2-JH2 linker domain of JAK2 has been implicated in the negative regulation of JAK2 activity. In 2 patients with myeloproliferative neoplasms (MPNs), we identified and characterized the novel JAK2 mutation S523L, which occurs in a key residue in the linker region. In 1 case, acquisition of JAK2S523L was associated with thrombocytosis and bone marrow megakaryocytic hyperplasia, and there were no other somatic alterations in this patient. The second patient with JAK2S523L mutation presented with increased hematocrit and had concurrent mutations in RUNX1 and BCORL1. Consistent with the genetic and clinical data, expression of JAK2S523L causes interleukin-3-independent growth in Ba/F3 cells transduced with the erythropoietin receptor by constitutively active Jak2/Stat5 signaling. © 2020 by The American Society of Hematology. |
| Keywords: | adult; clinical article; human tissue; middle aged; human cell; missense mutation; janus kinase 2; pathogenesis; case report; hypertension; genetic analysis; gene; gene expression; genetic association; hyperplasia; stat5 protein; erythropoietin receptor; myeloproliferative neoplasm; thrombocytosis; bone marrow disease; hematocrit; transcription factor runx1; interleukin 3; jak2 gene; erythrocytosis; high throughput sequencing; gain of function mutation; human; male; female; priority journal; article; runx1 gene; ba/f3 cell line; jak-stat signaling; bcorl1 gene; bone marrow megakaryocytic hyperplasia; jak2s523l gene |
| Journal Title: | Blood Advances |
| Volume: | 4 |
| Issue: | 18 |
| ISSN: | 2473-9529 |
| Publisher: | American Society of Hematology |
| Date Published: | 2020-09-22 |
| Start Page: | 4554 |
| End Page: | 4559 |
| Language: | English |
| DOI: | 10.1182/bloodadvances.2019001283 |
| PUBMED: | 32956452 |
| PROVIDER: | scopus |
| PMCID: | PMC7509885 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2020 -- Source: Scopus |
