真性红细胞增多症
红细胞生成
骨髓纤维化
突变体
缺铁
原发性血小板增多症
铁转运蛋白
表型
巨核细胞
生物
血红蛋白
造血
血小板增多症
内科学
骨髓增生性疾病
贫血
免疫学
海西定
医学
骨髓
干细胞
血小板
生物化学
基因
遗传学
作者
Jan Stetka,Marc Usart,Lucia Kubovčáková,Shivam Rai,Tata Nageswara Rao,Joshua Sutter,Hui Hao-Shen,Stefan Dirnhofer,Florian Geier,Michael S. Bader,Jakob Passweg,Vania Manolova,Franz Dürrenberger,Nouraiz Ahmed,Timm Schroeder,Tomas Ganz,Elizabeta Nemeth,Laura Silvestri,Antonella Nai,Clara Camaschella,Radek C. Skoda
出处
期刊:Blood
[American Society of Hematology]
日期:2023-02-09
被引量:5
标识
DOI:10.1182/blood.2022017976
摘要
JAK 2-V617F mutation causes myeloproliferative neoplasms (MPNs) that can manifest as polycythemia vera (PV), essential thrombocythemia (ET), or primary myelofibrosis. At diagnosis, patients with PV already exhibited iron deficiency, whereas patients with ET had normal iron stores. We examined the influence of iron availability on MPN phenotype in mice expressing JAK2-V617F and in mice expressing JAK2 with an N542-E543del mutation in exon 12 (E12). At baseline, on a control diet, all JAK2-mutant mouse models with a PV-like phenotype displayed iron deficiency, although E12 mice maintained more iron for augmented erythropoiesis than JAK2-V617F mutant mice. In contrast, JAK2-V617F mutant mice with an ET-like phenotype had normal iron stores comparable with that of wild-type (WT) mice. On a low-iron diet, JAK2-mutant mice and WT controls increased platelet production at the expense of erythrocytes. Mice with a PV phenotype responded to parenteral iron injections by decreasing platelet counts and further increasing hemoglobin and hematocrit, whereas no changes were observed in WT controls. Alterations of iron availability primarily affected the premegakaryocyte-erythrocyte progenitors, which constitute the iron-responsive stage of hematopoiesis in JAK2-mutant mice. The orally administered ferroportin inhibitor vamifeport and the minihepcidin PR73 normalized hematocrit and hemoglobin levels in JAK2-V617F and E12 mutant mouse models of PV, suggesting that ferroportin inhibitors and minihepcidins could be used in the treatment for patients with PV.
科研通智能强力驱动
Strongly Powered by AbleSci AI