Molecular Diagnosis and Prognosis of Multiple Myeloma

描述（由申请人提供）： 多发性骨髓瘤（MM）是一种致命的，克隆性B细胞恶性肿瘤， 分化的免疫球蛋白分泌浆细胞（PC），起源于 淋巴结的生殖中心，并在骨髓中生长和扩张。 虽然其他血液恶性肿瘤已被分子分类， 细胞遗传学异常，从历史上看，MM的分子分析一直是 难然而，使用高密度寡核苷酸DNA微阵列（HDA） 从高度纯化的PC中分离RNA的技术， 正常和恶性MM PC中近6800个基因， 未确定意义的丙种球蛋白病（MGUS）。 基于70多名新诊断的MM患者的初步数据， 7例MGUS病例，新的基于分子的诊断和预后模型， 将建立浆细胞恶液质MGUS和MM。这一目标将 通过三个具体目标实现。1.定义基因表达模式， 区分正常、肿瘤前和肿瘤性浆细胞。2.发展 利用基因表达建立MGUS和MM的诊断和预后模型 数据区. 3.定义疾病演变的分子特征， 耐药/复发通过纵向全球基因表达研究。一个新 MM和相关疾病的分子分类，通过 建议的工作，将使临床医生和板凳科学家更好地 在基因水平上理解和对抗浆细胞癌。这些知识 不仅能让我们更好地理解基本的生物学途径 在MM和MGUS中发生改变，但也将为 创建新的高度准确的分子测试来诊断和预测预后 也有助于设计新的治疗方法。因此 拟议的工作支持通过PAR-01-106资助的R33项目的目标 （创新技术在分子分析中的应用） 癌症）。

DESCRIPTION (provided by applicant): Multiple myeloma (MM) is a fatal, clonal B-cell malignancy of terminally differentiated immunoglobulin-secreting plasma cells (PCs) that originate in germinal centers of lymph nodes and home to and expand in the bone marrow. Although other hematological malignancies have been molecularly classified by cytogenetic abnormalities, historically, molecular analysis of MM has been difficult. However, using high-density oligonucleotide DNA microarray (HDA) technology on RNA isolated from highly purified PCs, expression profiles of nearly 6800 genes in normal and malignant MM PCs, as well as monoclonal gammopathy of undetermined significance (MGUS), have been established. Building on preliminary data from more than 70 newly diagnosed MM patients and 7 MGUS cases, new molecular-based diagnostic and prognostic models of the plasma cell dyscrasia MGUS and MM will be established. This goal will be accomplished through 3 specific aims. 1. Define gene expression patterns that differentiate normal, pre-neoplastic, and neoplastic plasma cells. 2. Develop diagnostic and prognostic models for MGUS and MM by use of gene expression profiles. 3. Define the molecular signatures of disease evolution and resistance/relapse through longitudinal global gene expression studies. A new molecular classification of MM and related disorders, provided through the proposed work, will enable clinicians and bench scientists to better understand and combat plasma cell cancer on a genetic level. This knowledge will not only allow a better under- standing of the basic biological pathways that are altered in MM and MGUS but also will provide the framework for the creation new highly accurate molecular tests to diagnose and predict prognosis of these diseases as well aid in the design of novel therapeutics. Thus, the work proposed supports the goals of an R33 project funded through PAR-01-106 (Applications of Innovative Technologies for the Molecular Analysis of Cancer).