Prevention of Chronic Lymphocytic Leukemia (CLL)

预防慢性淋巴细胞白血病 (CLL)

• 批准号: 7490723
• 负责人: MARC C. LEVESQUE
• 金额: $ 7.8万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7490723
• 关键词: Accounting; Adult; Autoimmune Diseases; B-Lymphocytes; Biological Markers; Blood; Blood specimen; Cell Separation; Cell surface; Cells; Cessation of life; Characteristics; Chromosome abnormality; Chronic Lymphocytic Leukemia; Clinical Treatment; Count; Development; Europe; Family; Family member; Flow Cytometry; Fluorescent in Situ Hybridization; Genes; Immunoglobulin Genes; Immunoglobulins; Lymphocyte Count; Lymphocytosis; Lymphoma; Memory B-Lymphocyte; Microarray Analysis; Morbidity - disease rate; Mutate; Nested PCR; North America; Numbers; Outcome; Patients; Phenotype; Pilot Projects; Population; Predisposing Factor; Prevention; Prevention strategy; Process; Prognostic Factor; Randomized Controlled Trials; Risk; Sampling; Somatic Mutation; Sorting - Cell Movement; Techniques; Testing; ZAP-70 Gene; disability; genetic pedigree; leukemia; member; mortality; outcome forecast; peripheral blood; prevent; rituximab; treatment trial

DESCRIPTION (provided by applicant): B-cell chronic lymphocytic leukemia (CLL) is one of the most common forms of leukemia in North America and Europe, accounting for approximately 30% of all cases. Monoclonal B cell lymphocytosis (MBL) has recently been recognized as a potential precursor to CLL and shares phenotypic characteristics with CLL. MBL is present in 3.5% of adults with normal blood counts and 40% of these subjects will have progressive increases in lymphocyte counts. Otherwise healthy subjects in families with 2 or more cases of CLL (familial CLL) have a 7-fold risk of MBL. This supports the hypothesis that there are common factors predisposing to CLL and MBL development and that MBL may be a precursor for CLL. Therefore, it is our hypothesis that identification of factors associated with the transition of MBL to CLL and aggressive early therapy to eradicate MBL in subjects at high risk of developing aggressive CLL with a poor prognosis may prevent death or disability. We believe that development of CLL prevention strategies that center on MBL as a precursor to CLL can be accomplished in three steps. The current application represents the first step in this three-step process. In the first step, phenotypic characteristics that may serve as surrogates for the transition of MBL to CLL will be identified in a pilot study by comparing MBL cells to CLL cells and by longitudinal analysis of MBL cell populations. To date, we have analyzed peripheral blood samples from 45 members of 6 pedigrees with familial CLL. These analyses identified 6 family members with MBL and 2 additional members with previously undiagnosed early CLL. We have developed techniques for analysis of immunoglobulin genes in single MBL cells using flow cytometry, cell sorting and nested PCR. We have also developed techniques for microarray analysis of limited numbers of B cells. We plan to use these and other techniques to perform a pilot study that will determine characteristics of MBL that are associated with transition to CLL by longitudinal analysis of samples from familial MBL subjects.

描述（由申请人提供）： B细胞慢性淋巴细胞性白血病（CLL）是北美和欧洲最常见的白血病形式之一，约占所有病例的30％。单克隆B细胞淋巴细胞增多症（MBL）最近被认为是CLL的潜在前体，并与CLL共享表型特征。 MBL存在于3.5％的血液计数正常的成年人中，其中40％的受试者将淋巴细胞计数逐渐增加。否则，有2例CLL病例（家族性CLL）的家庭中的健康受试者具有MBL的7倍。这支持了以下假设：CLL和MBL发育中存在常见的因素，并且MBL可能是CLL的前体。因此，我们的假设是，鉴定与MBL向CLL过渡和积极的早期治疗相关的因素，以消除具有高风险患有侵略性CLL的受试者的MBL，预后较差可能会阻止死亡或残疾。我们认为，可以通过三个步骤完成以MBL为中心的CLL预防策略的制定。当前的应用程序代表了此三步过程中的第一步。在第一步中，通过将MBL细胞与CLL细胞和MBL细胞群的纵向分析进行比较，可以在试点研究中确定可以作为MBL向CLL过渡到CLL的替代的表型特征。迄今为止，我们已经分析了来自家族性CLL的6个血统中45名成员的外周血样本。这些分析确定了6名具有MBL的家庭成员和2名先前未诊断的早期CLL的成员。我们开发了使用流式细胞仪，细胞分选和嵌套PCR分析单个MBL细胞中免疫球蛋白基因的技术。我们还开发了用于有限数量B细胞的微阵列分析的技术。我们计划使用这些技术和其他技术进行试验研究，该研究将通过对家族MBL受试者的样品进行纵向分析来确定与过渡到CLL相关的MBL特征。