Gene expression abnormalities in mycosis

描述（由申请方提供）：蕈样肉芽肿（MF）是一种皮肤归巢、记忆、CD 4 + T细胞的皮肤恶性肿瘤。这是一种临床表现多样且呈慢性进行性病程的疾病。随着疾病进展到晚期，肿瘤负荷增加，皮肤受累更广泛，导致全身性红皮病或发红。当异常的T细胞进入循环时，它被称为Sezary病。为了更好地了解这种复杂的皮肤恶性肿瘤，我们采取了分子方法，最初将我们的研究集中在Sezary患者的T细胞上，因为外周血中有丰富的肿瘤细胞。通过对Sezary病患者外周血单个核细胞（PBMC）的分析，我们发现了Sezary病患者肿瘤T细胞中细胞因子基因表达的严重缺陷。为了进一步研究基因表达异常的病因，我们采用了基因表达谱分析方法，假设正常T细胞和Sezary T细胞之间存在广泛的基因表达差异，这些差异导致了它们的分子和临床表型。使用来自正常个体和MF（Sezary）患者的纯化的T细胞的总RNA的高密度Affyphin寡核苷酸微阵列分析，我们发现了在Sezary T细胞中高度表达超过30倍的基因，以及在正常记忆T细胞中表达的优先丢失的基因。在这项提案中，我们将专注于一组在MF-Sezary T细胞中高度表达的基因，因为这些基因可能会让我们深入了解这种疾病，并可能改善诊断。该补助金的目的是：1。验证MF患者中的MF-Sezary基因。2.确定这些异常基因的表达在受影响组织中首次可检测到的疾病阶段。3.研究这些基因的表达是否通过体外和体内治疗而改变。

DESCRIPTION (provided by applicant): Mycosis fungoides (MF) is a cutaneous malignancy of skin homing, memory, CD4+ T cells. This is a disease with diverse clinical presentations and a chronic progressive course. As the disease progresses to later stages, there is increasing tumor burden with more extensive skin involvement, causing generalized erythroderma or redness with systemic involvement. When the abnormal T cells enter the circulation, it is known as Sezary disease. To gain a better understanding of this complex cutaneous malignancy, we have taken a molecular approach, initially focusing our studies on T cells from Sezary patients since there are abundant tumor cells in the peripheral blood. From analysis of peripheral blood mononuclear cells (PBMC) from patients with Sezary disease, we have identified profound cytokine gene expression defects in tumor T cells in patients with Sezary disease. To further study the etiology for gene expression abnormalities, we have taken a gene expression profiling approach, hypothesizing that there are extensive gene expression differences between normal T cells and Sezary T cells that account for their molecular and clinical phenotype. Using high-density Affymetrix oligonucleotide microarrary profiling of total RNA from purified T cells from normal individuals and from MF (Sezary) patients, we have discovered genes that are highly expressed by greater than 30-fold in Sezary T cells, as well as genes that are preferentially loss that are expressed in normal memory T cells. In this proposal, we will focus on a set of genes that are highly expressed in MF-Sezary T cells, as these may yield insight into this disease and may lead to improve diagnosis. The aim of this grant is: 1. To validate the MF-Sezary genes in MF patients. 2. To determine the stage of disease that the expression of these abnormal genes first become detectable in affected tissue. 3. To study whether the expression of these genes are altered by therapy in vitro and in vivo.