IL 2R SIGNALING PATHWAYS IN T CELL LYMPHOMA

T 细胞淋巴瘤中的 IL 2R 信号通路

• 批准号: 6030064
• 负责人: MARIUSZ A. WASIK
• 金额: $ 10万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6030064
• 关键词: T lymphocyte; biological signal transduction; cell line; cell proliferation; cytokine; cytokine receptors; flow cytometry; gel mobility shift assay; gene expression; interleukin 15; interleukin 2; lymphoma; messenger RNA; mycosis fungoides lymphoma; pathologic process; phosphoprotein phosphatase; phosphorylation; polymerase chain reaction; protein structure function; receptor binding; receptor expression; tissue /cell culture; transfection

DESCRIPTION: (adapted from the investigator's abstract) The purpose of this study is to investigate the role of cytokine mediated signal transduction pathway in the pathogenesis of human lymphomas. Specifically, the study will focus on the role of signals mediated through receptor for interleukin-2 (IL-2R) in the malignant transformation of T lymphocytes. Part of the IL-2R, common gamma chain (gamma c) is shared by receptors for several cytokines: IL-2, IL-4, IL-7, IL-9, and IL-15. Expression of the gamma c chain is essential for development and proliferation of normal T lymphocytes. In this study they will explore the expression, function and molecular structure of the gamma c and the cytokine-specific receptors which associate with gamma c by various types of malignant T-cell lymphoma. They will also examine whether the cytokines which signal through the cytokine receptors containing gamma c are synthesized and utilized by the malignant cells. Furthermore, they will study the expression, functional status, and structure of the IL-2R associated Jak/STAT signal transduction pathway as well as various, novel inhibitors of this pathway (members of the cytokine-receptor binding phosphatase, CIS/SOCS/SSI, and PIAS protein families). Finally, the expression, function, and structure of other molecles activated by IL-2R such as P13K, AKT, and STAM will also be determined. Particular attention will be paid to the possible differences in the IL-2R signaling between the indolent (low-grade/low stage) and aggressive (intermediate/high- grading/high state) variants of T-cell lymphoma. This study may result in a better understanding of the pathogenesis of at least some types of T-cell lymphoma. Consequently, it may lead to novel therapies for lymphoma based on selective inhibition of these elements of IL-2R signal transduction pathway(s) which are utilized by malignant T-cells.

描述：（改编自研究者摘要） 本研究的目的是探讨细胞因子的作用， 介导的信号转导通路在人类发病机制中的作用 淋巴瘤具体来说，这项研究将侧重于信号的作用， 通过白细胞介素2受体（IL-2R）介导的恶性 T淋巴细胞的转化。IL-2R的一部分，常见γ链 （γ c）由几种细胞因子的受体共享：IL-2，IL-4， IL-7、IL-9和IL-15。γ c链的表达对于 正常T淋巴细胞的发育和增殖。本研究 他们将探索的表达，功能和分子结构， γ C和与之相关的精氨酸特异性受体 各种类型的恶性T细胞淋巴瘤。他们还将 检测通过细胞因子传递信号的细胞因子 含有γ C的受体被合成并被利用， 恶性细胞此外，他们将研究表达，功能 IL-2R相关Jak/STAT信号的状态和结构 转导途径以及各种新的抑制剂， 途径（精氨酸受体结合磷酸酶的成员， CIS/SOCS/SSI和皮亚斯蛋白家族）。最后，表达式， 功能和结构的其他分子激活的IL-2R， P13K、AKT和STAM也将被确定。将特别注意 在IL-2R信号传导中， 惰性（低级/低级）和攻击性（中级/高级） 分级/高状态）T细胞淋巴瘤的变体。 这项研究可能会导致更好地了解的发病机制， 至少是某些类型的T细胞淋巴瘤因此，它可能导致 基于选择性抑制这些肿瘤的淋巴瘤的新疗法 IL-2R信号转导途径的元件，其被 恶性T细胞

项目成果

Lack of phosphotyrosine phosphatase SHP-1 expression in malignant T-cell lymphoma cells results from methylation of the SHP-1 promoter.

• DOI: 10.1016/s0002-9440(10)64629-9
• 发表时间: 2000-10
• 期刊: The American journal of pathology
• 作者: Q. Zhang;P. N. Raghunath;E. Vonderheid;N. Odum;M. Wasik