DYSREGULATED NFKB PATHWAY SIGNALING IN MYELOPROLIFERATIVE NEOPLASMS

骨髓增生性肿瘤中 NFKB 通路信号传导失调

基本信息

批准号：
10321938
负责人：
Stephen Tracy Oh
金额：
$ 41.37万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-12-11 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10321938
关键词：
Acute leukemia Address Antibodies Biological Assay Cessation of life Chronic Clinical Cytometry Data Development Disease Disease Progression Duct (organ) structure Evolution Hematologic Neoplasms Hematological Disease Hematopoietic stem cells Human Individual JAK2 gene Knock-in Knockout Mice Lead Maintenance Malignant - descriptor Monitor Morbidity - disease rate Mus Mutation Myelofibrosis Myelogenous Myeloproliferative disease NFKB Signaling Pathway Pathogenesis Pathway interactions Patients Pharmacology Polycythemia Vera Population Production Prognosis Property RELA gene Role Sampling Secondary acute myeloid leukemia Secondary to Signal Pathway Signal Transduction Stat5 protein Symptoms TNF gene TNFRSF1A gene TNFRSF1B gene Therapeutic Therapeutic Intervention Transplantation Tumor Necrosis Factor Receptor combinatorial cytokine effective therapy experimental study genetic manipulation in vivo inhibitor insight mortality mouse model p65 prevent reduce symptoms response retroviral transduction self-renewal therapy design

项目摘要

7. Project Summary/Abstract Myeloproliferative neoplasms (MPNs) are chronic blood disorders that that can cause severe symptoms and early death. New treatments have become available recently that help ameliorate symptoms, but they do not reliably slow or halt disease progression. We seek to better understand what drives disease development and progression in MPNs, so that we can develop better therapies for patients with these diseases. Our preliminary data indicates that a signaling pathway called the NFkB pathway is abnormally activated in MPNs. We hypothesize that this pathway contributes to the development and progression of MPNs. Therefore, we have proposed a combination of mouse and human studies to determine how the NFkB pathway contributes to MPN pathogenesis, and to evaluate whether inhibition of NFkB signaling may have potential therapeutic benefits for MPN patients.

7. 项目总结/摘要骨髓增生性肿瘤 (MPN) 是一种慢性血液疾病，可导致严重的症状和早逝。最近出现了有助于改善症状的新疗法，但它们并不能可靠地减缓或阻止疾病进展。我们寻求更好地了解疾病发展的驱动因素以及 MPN 的进展，以便我们能够为患有这些疾病的患者开发更好的疗法。我们的初步数据表明，一种称为 NFkB 通路的信号通路在 MPN。我们假设该途径有助于 MPN 的发展和进展。所以，我们提出了小鼠和人类研究的结合来确定 NFkB 通路如何有助于 MPN 发病机制，并评估抑制 NFkB 信号传导是否具有潜力 MPN 患者的治疗益处。