Intracellular Signaling in Malignant Lymphoma Cells

恶性淋巴瘤细胞的细胞内信号转导

基本信息

批准号：
7616158
负责人：
GARRY P NOLAN
金额：
$ 39.66万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7616158
关键词：
Address Apoptosis Apoptotic B-Cell Neoplasm Biochemical Biological Assay Cell Line Cell Lineage Cells Classification Clinical Clinical Distribution Complex Condition Disease Disease Outcome Event Flow Cytometry Follicular Lymphoma Goals Hematologic Neoplasms Heterogeneity Human Immune Immune system In Vitro Individual Kinetics Link Lymphoma Lymphomagenesis Maps Measures Molecular Molecular Abnormality Molecular Genetics Mutation Myeloid Leukemia Nature Neoplasms Non-Hodgkin&apos s Lymphoma Oncogenes Outcome Pathway interactions Patients Pattern Phenotype Phospho-Specific Antibodies Phosphorylation Population Proteins Range Relapse Relative (related person)Research Personnel Risk Sampling Signal Transduction Specimen Standards of Weights and Measures Taxonomy Testing Training Treatment Protocols Work base cell killing chemotherapy host neoplasm interaction large cell Diffuse non-Hodgkin&apos s lymphoma neoplastic cell outcome forecast predictive modeling programs response tumor tumor progression

项目摘要

Changes in intracellular protein levels, subcellular localization, or activation state are considered to be reflective of a cell's capabilities or functions. Some of these events are relatively transitory - such as some phosphorylation of proteins in cell signaling cascades. Some of the relevant cell populations are so rare as to make their isolation for standard biochemical analysis nearly impossible. Remodeling of such cell signaling mechanisms drives tumor proliferation and suppresses apoptosis, contributing to tumor survival despite intense therapy regimens. Therefore, to understand how signaling networks are remodeled in hematological tumors there is a need to measure complex populations of immune system cells and phenotype them not only for their cell lineage status but also for their relative activation state. The central hypothesis of these studies is that patients whose tumors share similar mechanisms of proliferative and anti-apoptotic signaling will respond similarly to a defined tumor cell killing regimen. Underlying this idea is the additional hypothesis that heritable differences among tumors will detectably modify tumor cell signaling networks. A long range goal in this project is to develop a predictive model of FL clinical outcome based on molecular mechanisms of signaling detected in heterogeneous tumor cell populations. In addressing this goal, we will a) construct a signaling taxonomy of FL, b) delineate remodeled signaling mechanisms in FL tumor cells, and c) correlate profiles of signaling in lymphoma with both heritable changes in tumors and clinical measures of disease aggressiveness. We will also test the hypothesis that cell by cell enumeration of signaling mechanisms will reveal the nature of the tumor - host interaction and distinguish tumor cell subsets whose presence and signaling state correlate with disease outcome.

细胞内蛋白质水平，亚细胞定位或激活状态的变化被认为是反射的单元的功能或功能。其中一些事件是相对暂时的 - 例如一些磷酸化细胞信号级联中的蛋白质。一些相关的细胞群体非常罕见，以至于将它们的隔离用于标准生化分析几乎不可能。这种细胞信号的重塑机制驱动肿瘤增殖并抑制凋亡，尽管强烈治疗方案。因此，了解如何在血液学中重塑信号网络肿瘤需要测量免疫系统细胞的复杂种群，而不是表型仅出于其细胞谱系状态，也仅用于其相对激活状态。这些研究的核心假设是，肿瘤具有相似机制的患者增殖的患者抗凋亡信号传导将对定义的肿瘤细胞杀伤方案做出类似的反应。基础想法是另一种假设，即肿瘤之间可遗传的差异将可检测到肿瘤细胞信号网络。该项目的远距离目标是开发FL临床结果的预测模型基于在异质肿瘤细胞种群中检测到的信号传导的分子机制。在寻址这个目标，我们将a）构建FL的信号分类法，b）描述重塑的信号传导机制在FL肿瘤细胞中，c）将淋巴瘤信号传导的特征与肿瘤的两个可遗传变化相关和疾病侵略性的临床指标。我们还将测试通过细胞枚举细胞的假设信号传导机制的性质将揭示肿瘤的性质 - 宿主相互作用并区分肿瘤细胞存在和信号状态与疾病结果相关的子集。