Molecular Pathways in T Cell Development and Thymic Lymphoma

T 细胞发育和胸腺淋巴瘤的分子途径

• 批准号: 6989689
• 负责人: HARALD VON BOEHMER
• 金额: $ 21.01万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-11 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6989689
• 关键词: T cell receptor; T lymphocyte; acute lymphocytic leukemia; athymic mouse; biological signal transduction; carcinogenesis; cell differentiation; cell growth regulation; cytogenetics; flow cytometry; gene expression; gene expression profiling; genetically modified animals; human T cell leukemia; laboratory mouse; leukocyte activation /transformation; lymphoma; microarray technology; molecular oncology; polymerase chain reaction; thymus neoplasms; transcription factor; western blottings

DESCRIPTION (provided by applicant): Intrathymic T cell development proceeds through receptor- controlled checkpoints at which cells with properly assembled T cell receptors (TCR) are rescued from programmed cell death, expand and/or undergo further differentiation. Differentiation is controlled by transcription factors such as Notch1-dependent CSL, Ikaros, b-catenin-dependent TCF1 as well as basic helix loop helix (bHLH) proteins encoded by E2A and HEB genes. Some of the transcription factors control the assembly of the pre-TCR and signaling by the pre-TCR can regulate the function of certain transcription factors. While the binding of E47/HEB heterodimers to E-boxes in the regulatory region of several genes is believed to induce differentiation at the expense of proliferation, interference with that process is believed to result in proliferation at the expense of differentiation. Within this frame we will address the hypotheses that 1) Lymphomagenic abnormalities in gene expression synergize with the pre-TCR in generating T-ALL, 2) that known abnormalities in gene expression resulting in lymphoma affect cell cycle/survival of developing T cells, 3) that in the generation of T-ALL initial abnormalities in gene expression must be followed by further genetic changes, and 4) that similar molecular pathways are involved in murine and human T-ALL over expressing TALl.

描述（由申请人提供）：胸腺内T细胞的发育通过受体-进行