Prevalence and Progression of Monoclonal Gammopathies

单克隆丙种球蛋白病的患病率和进展

• 批准号: 7184379
• 负责人: S VINCENT RAJKUMAR
• 金额: $ 28.67万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7184379
• 关键词: 2-methoxyestradiol; Accounting; Address; Adverse effects; Affect; Age; Alkylating Agents; American; Anemia; Archives; Autologous Stem Cell Transplantation; B lymphoid malignancy; Biological Assay; Biological Response Modifier Therapy; Biology; Blood; Blood Circulation; Bone Marrow; CC-5013; CD34 gene; Cell Adhesion Molecules; Clinic; Clinical; Clinical Trials Design; Coin; Condition; County; Data; Databases; Detection; Diagnosis; Disease; Dose; Elderly; Epidemiology; Equilibrium; Evaluation; Event; Family; First Degree Relative; Flow Cytometry; Funding; Future; Gender; Genes; Genetic; Genetic Polymorphism; Goals; Grant; Heavy-Chain Immunoglobulins; Hematologic Neoplasms; High Prevalence; Hypercalcemia; Immunohistochemistry; Incidence; Inherited; Interleukin-1 beta; Intervention; Kidney Failure; Laboratories; Lesion; Life; Light; Light-Chain Immunoglobulins; Link; Longevity; Lytic; Lytic Lesion; Malignant - descriptor; Malignant Neoplasms; Marrow; Mediator of activation protein; Minnesota; Modality; Molecular Genetics; Monitor; Monoclonal Gammapathies; Monoclonal gammopathy of uncertain significance; Multiple Myeloma; Natural History; Nature; Non-Malignant; Pathogenesis; Patients; Plasma Cells; Play; Population; Population Control; Precancerous Conditions; Predictive Value of Tests; Predisposing Factor; Predisposition; Premalignant; Prevalence; Prevalence Study; Prevention; Prevention strategy; Preventive; Proteins; Rate; Reporting; Research Personnel; Rheumatoid Arthritis; Risk; Risk Factors; Role; Sampling; Serum; Siblings; Staging; Surveys; Techniques; Testing; Thalidomide; Therapeutic; Time; Uncertainty; United States; aged; angiogenesis; base; bisphosphonate; bone; chemotherapy; cytotoxic; density; follow-up; insight; melanoma; migration; multiple myeloma M Protein; neoplastic cell; outcome forecast; prevent; programs; size; trait

DESCRIPTION (provided by applicant): Multiple myeloma evolves from a premalignant condition called monoclonal gammopathy of undetermined significance (MGUS). This project has defined the prevalence of MGUS, the risk of progression of MGUS to MM, risk factors for progression, and association of MGUS with other diseases. Since MM is incurable, it is imperative to understand and characterize its premalignant stages so interventions that prevent or delay progression of MGUS to MM are possible. To achieve our goal of understanding and targeting the progression of MGUS to MM, we identified 3 crucial questions that must be addressed: 1) what are the additional predictors of progression that can define a subset of MGUS patients with a risk of progression high enough to warrant intervention? (MGUS has a 1% per year risk of progression. In the preceding funding period we identified risk factors that increase this risk to 3-4% per year. With studies proposed in this grant our goal is to identify a high-risk group with a 10% risk of progression per year); 2) what is the premalignant stage responsible for up to 20% of MM (light chain MM) that is not preceded by MGUS?; and 3) what role do genetic or familial factors play in MGUS? Our Specific Aims correspond to these 3 key questions. In Aim 1, we will test the predictive value of 3 key factors chosen based on specific hypotheses, our understanding of the MGUS biology, and based on preliminary data. They are: monoclonal free light chains detected by a sensitive serum based assay, circulating plasma cells detected by immunofluorescent assay/flow cytometry and microvessel density by CD34 immunohistochemistry. In Aim 2 we will study the precursor lesion for 20% of MM (light chain MM) that is not preceded by typical MGUS. We hypothesize and have preliminary data for the presence of a new entity called light chain MGUS that leads to light chain MM. We will study the prevalence, risk of progression, and predictors of progression and survival of light chain MGUS in a population based study using serum samples from over 21,000 residents of Olmsted County. Finally in Aim 3, we will study the prevalence of MGUS in first-degree relatives of Olmsted County residents with known MGUS. We have preliminary data that there is familial clustering of MGUS, and familial incidence of MM has been reported. Families in which 3 or more first degree relatives are affected with MGUS are candidates for collaborative studies to look for genetic polymorphisms that predispose to MGUS.

描述（由申请人提供）：多发性骨髓瘤从称为单克隆肾上腺病的疾病中演变出来，具有不确定的意义（MGU）。该项目定义了MGU的患病率，MGU向MM的发展风险，进展的危险因素以及MGU与其他疾病的关联。由于MM无法治愈，因此必须理解和表征其前临时阶段，因此可以防止或延迟MGU向MM进展的干预措施。为了实现我们理解和定位MGU向MM发展的目标，我们确定了3个必须解决的关键问题：1）进展的其他预测因素是什么，可以定义有足够高的进展风险以保证干预的MGUS患者的子集？ （MGUS每年有1％的进步风险。在上一个融资期内，我们确定了将这种风险增加到每年3-4％的风险因素。随着该赠款的研究，我们的目标是确定一个高风险群体，其每年的进展风险为10％）； 2）什么是在不含Mgus之前的MM（轻链MM）20％（轻链MM）的情况？ 3）遗传因素或家族因素在MGU中起什么作用？我们的具体目标对应于这3个关键问题。在AIM 1中，我们将根据特定假设，我们对MGUS生物学的理解以及基于初步数据选择的3个关键因素的预测值。它们是：通过基于敏感的血清测定法检测到的单克隆游离光链，通过免疫荧光测定/流式细胞仪检测到的循环浆细胞和通过CD34免疫组织化学检测到的微血管密度。在AIM 2中，我们将研究前体病变的20％的MM（轻链MM），而不是典型的MGU。我们假设并具有初步数据，用于存在导致轻链MM的新实体，称为轻链MGU。我们将研究基于人群的研究中使用来自Olmsted县的21,000多名居民的血清样本的轻型链MGU的进展和存活预测的患病率，进展风险以及轻链MGU的进展和存活率。最终，在AIM 3中，我们将研究以已知MGU的Olmsted County居民一级亲戚的MGU患病率。我们有初步的数据表明，MGU有家族性聚类，并且已经报道了MM的家族性发生率。 3个或多个一级亲戚受MGU影响的家庭是合作研究的候选者，以寻找容易发生MGU的遗传多态性。