| Title: |
IDH2 mutation accelerates TPO‐induced myelofibrosis with enhanced S100a8/a9 and NFκB signaling in vivo |
| Authors: |
Chien‐Chin Lin, Chi‐Yuan Yao, Yu‐Hung Wang, Yueh‐Chwen Hsu, Chang‐Tsu Yuan, Tsung‐Chih Chen, Chia‐Lang Hsu, Sze‐Hwei Lee, Jhih‐Yi Lee, Pin‐Tsen Shih, Chein‐Jun Kao, Po‐Han Chuang, Yuan‐Yeh Kuo, Hsin‐An Hou, Wen‐Chien Chou, Hwei‐Fang Tien |
| Source: |
eJHaem, Vol 5, Iss 4, Pp 738-748 (2024) |
| Publisher Information: |
Wiley, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Diseases of the blood and blood-forming organs |
| Subject Terms: |
IDH2 mutation, myelofibrosis, S100a8/a9, TPO, Diseases of the blood and blood-forming organs, RC633-647.5 |
| More Details: |
Abstract Introduction IDH2 mutation is an unfavorable prognostic factor in patients with primary myelofibrosis (PMF) but its effect on myelofibrosis (MF) remains largely unclear. Methods In this study, we aimed to elucidate the roles of IDH2 mutation in the development and progression of MF by transcriptomic and molecular techniques using the Idh2R172K transgenic mice. Results We found that thrombopoietin (TPO)‐overexpressed Idh2R172K (Idh2R172K + TPO) mice had accelerated progression to MF, compared with TPO‐overexpressed Idh2‐wild (WT + TPO) mice, showing activation of multiple inflammatory pathways, among which nuclear factor κB (NFκB) was the most significantly enhanced. Single‐cell transcriptomes of the marrow cells in early MF showed that S100a8/a9 expression was mainly confined to neutrophil progenitors in the WT + TPO mice, but highly expressed in several types of myeloid precursor cells, including the megakaryocyte progenitors in the Idh2R172K + TPO group. Furthermore, Idh2R172K mice at age of 18 months had larger spleens, increased S100a8/a9‐Tlr4 expression, and elevated serum S100a8/a9 levels compared with WT mice. PMF patients with IDH2 mutations had higher bone marrow plasma S100A8/A9 levels than those without IDH2 mutations. Conclusion Overall, our findings showed that IDH2 mutation induced proinflammatory effects, which further exacerbated MF, as evidenced by the increase in S100a8/a9 levels and NFκB hyperactivation in Idh2R172K + TPO mice. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2688-6146 |
| Relation: |
https://doaj.org/toc/2688-6146 |
| DOI: |
10.1002/jha2.983 |
| Access URL: |
https://doaj.org/article/fa92d941b488439f9510b04086ba0152 |
| Accession Number: |
edsdoj.fa92d941b488439f9510b04086ba0152 |
| Database: |
Directory of Open Access Journals |
