Characterization of regulatory and target pathways of microRNAs downstream of the leukemogeneic Hoxa9/Meis1 axis (A05)

白血病 Hoxa9/Meis1 轴下游 microRNA 的调控和靶标途径的表征 (A05)

• 批准号: 223083472
• 金额: --
• 依托单位: BC Cancer Research Centre
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/223083472?language=en
• 关键词: Characterization; regulatory; target; pathways; microRNAs

Based on our results from the first funding period, we will investigate the role, regulation and downstream targets of miR-155 and miR-708 in Hoxa9/Meis1-driven acute myeloid leukemia (AML). In addition, we will extend our analysis to the Leukemia-Initiating Cell (LIC) enriched compartment of Hoxa9/Meis1 cells at the transcriptional and proteomic level. Finally, considering the clinically relevant but not fully understood relevance of Hoxa9 and Meis1 in acute lymphoblastic leukemia (ALL), we will dissect their role in ALL through establishing a novel ALL mouse transplantation model based on the overexpression of Hoxa9/Meis1 in lymphoid conditions. Overall goal of our proposal is to define Hoxa9/Meis1 associated pathways in acute leukemias and uncover novel therapeutic targets.

基于我们第一个资助期的结果，我们将研究miR-155和miR-708在Hoxa 9/Meis 1驱动的急性髓系白血病（AML）中的作用、调控和下游靶点。此外，我们将扩展我们的分析，以白血病启动细胞（LIC）丰富的车厢Hoxa 9/Meis 1细胞在转录和蛋白质组水平。最后，考虑到Hoxa 9和Meis 1在急性淋巴细胞白血病（ALL）中的临床相关性，但尚未完全了解其相关性，我们将通过建立一种基于Hoxa 9/Meis 1在淋巴条件下过表达的新型ALL小鼠移植模型来剖析它们在ALL中的作用。我们的提案的总体目标是确定Hoxa 9/Meis 1相关的途径在急性白血病和发现新的治疗靶点。