SRSF2 mutation reduces polycythemia and impairs hematopoietic progenitor functions in JAK2V617F-driven myeloproliferative neoplasm
Abstract SRSF2 mutations are found in association with JAK2V617F in myeloproliferative neoplasms (MPN), most frequently in myelofibrosis (MF). However, the contribution of SRSF2 mutation in JAK2V617F-driven MPN remains elusive. To investigate the consequences of SRSF2P95H and JAK2V617F mutations in...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-11-01
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| Series: | Blood Cancer Journal |
| Online Access: | https://doi.org/10.1038/s41408-023-00947-y |
| _version_ | 1827604311897538560 |
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| author | Yue Yang Salar Abbas Mohammad A. Sayem Avik Dutta Golam Mohi |
| author_facet | Yue Yang Salar Abbas Mohammad A. Sayem Avik Dutta Golam Mohi |
| author_sort | Yue Yang |
| collection | DOAJ |
| description | Abstract SRSF2 mutations are found in association with JAK2V617F in myeloproliferative neoplasms (MPN), most frequently in myelofibrosis (MF). However, the contribution of SRSF2 mutation in JAK2V617F-driven MPN remains elusive. To investigate the consequences of SRSF2P95H and JAK2V617F mutations in MPN, we generated Cre-inducible Srsf2P95H/+Jak2V617F/+ knock-in mice. We show that co-expression of Srsf2P95H mutant reduced red blood cell, neutrophil, and platelet counts, attenuated splenomegaly but did not induce bone marrow fibrosis in Jak2V617F/+ mice. Furthermore, co-expression of Srsf2P95H diminished the competitiveness of Jak2V617F mutant hematopoietic stem/progenitor cells. We found that Srsf2P95H mutant reduced the TGF-β levels but increased the expression of S100A8 and S100A9 in Jak2V617F/+ mice. Furthermore, enforced expression of S100A9 in Jak2V617F/+ mice bone marrow significantly reduced the red blood cell, hemoglobin, and hematocrit levels. Overall, these data suggest that concurrent expression of Srsf2P95H and Jak2V617F mutants reduces erythropoiesis but does not promote the development of bone marrow fibrosis in mice. |
| first_indexed | 2024-03-09T05:57:15Z |
| format | Article |
| id | doaj.art-6902006d5db34f2a8395ff87f0083968 |
| institution | Directory Open Access Journal |
| issn | 2044-5385 |
| language | English |
| last_indexed | 2024-03-09T05:57:15Z |
| publishDate | 2023-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Blood Cancer Journal |
| spelling | doaj.art-6902006d5db34f2a8395ff87f00839682023-12-03T12:12:14ZengNature Publishing GroupBlood Cancer Journal2044-53852023-11-0113111010.1038/s41408-023-00947-ySRSF2 mutation reduces polycythemia and impairs hematopoietic progenitor functions in JAK2V617F-driven myeloproliferative neoplasmYue Yang0Salar Abbas1Mohammad A. Sayem2Avik Dutta3Golam Mohi4Department of Biochemistry and Molecular Genetics, University of Virginia School of MedicineDepartment of Biochemistry and Molecular Genetics, University of Virginia School of MedicineDepartment of Biochemistry and Molecular Genetics, University of Virginia School of MedicineDepartment of Biochemistry and Molecular Genetics, University of Virginia School of MedicineDepartment of Biochemistry and Molecular Genetics, University of Virginia School of MedicineAbstract SRSF2 mutations are found in association with JAK2V617F in myeloproliferative neoplasms (MPN), most frequently in myelofibrosis (MF). However, the contribution of SRSF2 mutation in JAK2V617F-driven MPN remains elusive. To investigate the consequences of SRSF2P95H and JAK2V617F mutations in MPN, we generated Cre-inducible Srsf2P95H/+Jak2V617F/+ knock-in mice. We show that co-expression of Srsf2P95H mutant reduced red blood cell, neutrophil, and platelet counts, attenuated splenomegaly but did not induce bone marrow fibrosis in Jak2V617F/+ mice. Furthermore, co-expression of Srsf2P95H diminished the competitiveness of Jak2V617F mutant hematopoietic stem/progenitor cells. We found that Srsf2P95H mutant reduced the TGF-β levels but increased the expression of S100A8 and S100A9 in Jak2V617F/+ mice. Furthermore, enforced expression of S100A9 in Jak2V617F/+ mice bone marrow significantly reduced the red blood cell, hemoglobin, and hematocrit levels. Overall, these data suggest that concurrent expression of Srsf2P95H and Jak2V617F mutants reduces erythropoiesis but does not promote the development of bone marrow fibrosis in mice.https://doi.org/10.1038/s41408-023-00947-y |
| spellingShingle | Yue Yang Salar Abbas Mohammad A. Sayem Avik Dutta Golam Mohi SRSF2 mutation reduces polycythemia and impairs hematopoietic progenitor functions in JAK2V617F-driven myeloproliferative neoplasm Blood Cancer Journal |
| title | SRSF2 mutation reduces polycythemia and impairs hematopoietic progenitor functions in JAK2V617F-driven myeloproliferative neoplasm |
| title_full | SRSF2 mutation reduces polycythemia and impairs hematopoietic progenitor functions in JAK2V617F-driven myeloproliferative neoplasm |
| title_fullStr | SRSF2 mutation reduces polycythemia and impairs hematopoietic progenitor functions in JAK2V617F-driven myeloproliferative neoplasm |
| title_full_unstemmed | SRSF2 mutation reduces polycythemia and impairs hematopoietic progenitor functions in JAK2V617F-driven myeloproliferative neoplasm |
| title_short | SRSF2 mutation reduces polycythemia and impairs hematopoietic progenitor functions in JAK2V617F-driven myeloproliferative neoplasm |
| title_sort | srsf2 mutation reduces polycythemia and impairs hematopoietic progenitor functions in jak2v617f driven myeloproliferative neoplasm |
| url | https://doi.org/10.1038/s41408-023-00947-y |
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