Division of Hematology, Department of Pediatrics, The Children's Hospital of Philadelphia (CHOP), Philadelphia, PA, United States of America.
Ionis Pharmaceuticals, Inc., Carlsbad, CA, United States of America.
PLoS One. 2021 Dec 10;16(12):e0251995. doi: 10.1371/journal.pone.0251995. eCollection 2021.
Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm resulting from an acquired driver mutation in the JAK2 gene of hematopoietic stem and progenitor cells resulting in the overproduction of mature erythrocytes and abnormally high hematocrit, in turn leading to thromboembolic complications. Therapeutic phlebotomy is the most common treatment to reduce the hematocrit levels and consequently decrease thromboembolic risk. Here we demonstrate that, by using the iron restrictive properties of the antisense oligonucleotides against Tmprss6 mRNA, we can increase hepcidin to achieve effects equivalent to therapeutic phlebotomy. We provide evidence that this less invasive approach could represent an additional therapeutic tool for the treatment of PV patients.
真性红细胞增多症 (PV) 是一种慢性骨髓增殖性肿瘤，由造血干细胞和祖细胞中 JAK2 基因的获得性驱动突变引起，导致成熟红细胞过度生成和异常高的血细胞比容，进而导致血栓栓塞并发症。治疗性放血是降低血细胞比容水平、降低血栓栓塞风险的最常见治疗方法。在这里，我们证明通过利用针对 Tmprss6 mRNA 的反义寡核苷酸的铁限制特性，我们可以增加铁调素以达到与治疗性放血相当的效果。我们提供的证据表明，这种侵入性较小的方法可能成为治疗 PV 患者的另一种治疗工具。
