文章：

SRSF2突变在JAK2V617F驱动的骨髓增殖性肿瘤中减轻红细胞增多症并损害造血祖细胞功能

SRSF2 mutation reduces polycythemia and impairs hematopoietic progenitor functions in JAK2V617F-driven myeloproliferative neoplasm

原文发布日期：2023-11-27

DOI: 10.1038/s41408-023-00947-y

类型: Article

开放获取: 是

英文摘要：

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.
 

摘要翻译： 

在骨髓增殖性肿瘤中，SRSF2突变常与JAK2V617F突变共存，尤其在骨髓纤维化中最为常见。然而，SRSF2突变在JAK2V617F驱动的骨髓增殖性肿瘤中的作用尚不明确。为探究SRSF2P95H与JAK2V617F突变在骨髓增殖性肿瘤中的影响，我们构建了Cre诱导型Srsf2P95H/+Jak2V617F/+基因敲入小鼠。研究发现，Srsf2P95H突变体的共表达降低了Jak2V617F/+小鼠的红细胞、中性粒细胞及血小板计数，减轻了脾肿大，但未诱发骨髓纤维化。此外，Srsf2P95H的共表达削弱了Jak2V617F突变造血干细胞/祖细胞的竞争能力。我们发现Srsf2P95H突变降低了Jak2V617F/+小鼠的TGF-β水平，但增加了S100A8和S100A9的表达。进一步在Jak2V617F/+小鼠骨髓中强制表达S100A9，可显著降低红细胞、血红蛋白和红细胞比容水平。总体而言，这些数据表明Srsf2P95H与Jak2V617F突变体的共表达会抑制红细胞生成，但并未促进小鼠骨髓纤维化的发展。

原文链接：

SRSF2 mutation reduces polycythemia and impairs hematopoietic progenitor functions in JAK2V617F-driven myeloproliferative neoplasm