Aberrant activation of β1 and β2 integrins on leukocytes in JAK2-V617F mutated disease (A20)

JAK2-V617F 突变疾病 (A20) 白细胞上 β1 和 β2 整合素的异常激活

• 批准号: 186636103
• 金额: --
• 依托单位: Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/186636103?language=en
• 关键词: Aberrant; activation; integrins; leukocytes; JAK2

A20 investigates the activation of integrins on leukocytes in JAK2-V617F-positive chronic myeloproliferative neoplasia (CMN). JAK2-mutated CMN is characterized by clonal proliferation of myeloid cells and a striking inflammatory syndrome. In the previous funding period, we found that JAK2-V617F aberrantly activates β1 and β2 integrins (VLA4 and LFA1) on leukocytes in CMN and identified the molecular mechanisms involved. Using the Vav1-Cre x JAK2+/V617F knock-in mouse model established in our laboratory, we aim to dissect the contribution of aberrant integrin activation for the JAK2-V617F- induced cytokine dysregulation, splenomegaly and pro-thrombotic state.

A20研究了JAK2-V617F阳性慢性骨髓增生性肿瘤(CMN)患者白细胞上整合素的激活情况。JAK2突变的CMN以髓系细胞克隆性增殖和显著的炎症综合征为特征。在前期的研究中，我们发现JAK2-V617F能异常激活巨噬细胞中白细胞表面的β-1和β-2整合素，并对其分子机制进行了研究。利用本实验室建立的Vav1-Cre x JAK2+/V617F敲入小鼠模型，分析整合素的异常激活在JAK2-V617F诱导的细胞因子失调、脾肿大和血栓前状态中的作用。