Role of FBXO45 in Diffuse Large B Cell Lymphoma Pathogenesis

FBXO45 在弥漫性大 B 细胞淋巴瘤发病机制中的作用

基本信息

批准号：
10703746
负责人：
KOJO S. J. ELENITOBA-JOHNSON
金额：
$ 51.11万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-10-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10703746
关键词：
3q29 Affinity Affinity Chromatography B cell differentiation B-Cell Development B-Cell Lymphomas B-Lymphocyte Subsets B-Lymphocytes BCL2 gene BCL6 gene Biochemical Biological Biological Process Birth Cancer Etiology Cell Differentiation process Cell Line Cell physiology Cells Cellular biology Cessation of life Characteristics Clustered Regularly Interspaced Short Palindromic Repeats Communities Complement Constitutional Cullin Proteins Data Development Event F Box Domain Family Gene Targeting Genes Genetic Genomics Growth Guanine Nucleotide Exchange Factors Hour Human Knock-in Knock-out Lymphoma Lymphomagenesis MS4A1 gene Malignant Neoplasms Mediating Molecular Molecular Biology Techniques Mus Mutagenesis Neoplasms Oncogenic Pathogenesis Pharmacology Play Proteolysis Proteomics RNA RNA Interference Recurrence Research Resources Role Sampling Structure of germinal center of lymph node Tamoxifen Testing Time Transgenic Mice Tumor Suppressor Genes Tumor Suppressor Proteins Tumorigenicity Ubiquitin-mediated Proteolysis Pathway Update Xenograft Model cohort genome sequencing in vivo insight large cell Diffuse non-Hodgkin&apos s lymphoma member mouse model novel novel therapeutic intervention prognostic proteogenomics screening small hairpin RNA tandem mass spectrometry targeted treatment treatment strategy ubiquitin ligase ubiquitin-protein ligase whole genome

项目摘要

PROJECT SUMMARY THE ROLE OF FBXO45 IN DIFFUSE LARGE B-CELL LYMPHOMA PATHOGENESIS Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma and represents the most common form of malignant lymphoma in the western hemisphere. The biologic events underlying the pathogenesis of DLBCL are not completely understood. We have recently identified functional inactivation of FBXO45, an E3 ubiquitin ligase in DLBCL. In this application, we will utilize transgenic mouse models to explore the biological roles for FBXO45 in B-cell differentiation and lymphomagenesis. Further, we will employ biochemical and molecular biology techniques to better understand the role FBXO45 in the pathogenesis of DLBCL. Accordingly, we propose in the first aim of this application to utilize newly created transgenic mouse models to functionally interrogate the role of FBXO45 in B- cell development and lymphomagenesis. In the second aim, we will identify the global cellular substrates of FBXO45 in B cell contexts. These studies will establish the role of FBXO45 in the pathogenesis of DLBCL and establish the mechanisms by which its deregulation contributes to DLBCL.

项目摘要 FBXO45在扩散的大B细胞淋巴瘤发病机理中的作用弥漫性大B细胞淋巴瘤（DLBCL）是一种侵袭性淋巴瘤，代表西半球最常见的恶性淋巴瘤。生物事件 DLBCL的发病机理的基础尚未完全理解。我们最近有鉴定出DLBCL中的E3泛素连接酶的FBXO45的功能失活。在这个应用，我们将利用转基因小鼠模型探索生物学作用 B细胞分化和淋巴作用中的FBXO45。此外，我们将雇用生化和分子生物学技术，以更好地了解FBXO45的作用 DLBCL的发病机理。因此，我们在本申请的第一个目的中提出了使用新创建的转基因小鼠模型在功能上询问FBXO45在B-中的作用细胞发育和淋巴作用。在第二个目标中，我们将确定全球 B细胞环境中FBXO45的细胞底物。这些研究将确定 fbxo45在DLBCL的发病机理中，并建立了它的机制放松管制有助于DLBCL。