Prevalence, etiology, and clinical implications of low count monoclonal B-cell lymphocytosis (MBL)

项目摘要 我们的建议解决了定义低计数单克隆B临床后果的重要问题 细胞淋巴细胞增多症（LC MBL），并深入了解为什么5%-10%的40岁以上的美国成年人 这个条件。 MBL -慢性淋巴细胞白血病（CLL）的前体状态，是最常见的癌前病变之一 人类的条件。MBL患者具有循环克隆B细胞群，绝对B细胞计数 <5x 109/L，无淋巴组织增生性疾病的其他特征。研究发现， MBL随着年龄的增长而增加，影响40岁以下个体的<0.5%，40-60岁个体的5%， 60岁以上的人。MBL现在被细分为低计数（LC）MBL和高计数（HC）MBL，这取决于 绝对B细胞计数是否高于或低于1 × 109/L。绝大多数（>98%） 患有MBL的个体患有LC MBL并且从未引起临床注意。LC MBL的临床后果 大部分都是未知的。尽管进展为CLL的风险较低，但患有LC MBL的个体很可能患有 其他重要的临床后果。 在对1001名年龄>40岁的成年人进行的初步研究中，我们发现LC MBL患者总体上减少了 存活率和威胁生命的感染风险增加。这表明，5%-10%的40岁以上的成年人有一个 大部分未经研究的、获得性的、无症状的具有潜在重要临床意义的病症。目前 关于发生MBL的风险因素，几乎没有任何信息。我们现在通过这个 确定LC MBL在感染风险方面的关键临床后果的提案 和非血液学恶性肿瘤，并确定发生LC MBL的风险因素。这是 因为我们有独特的机会使用马约诊所生物库研究MBL，这是世界上唯一的组织库。 我们知道，美国以允许测试的方式储存外周血单核细胞， LC MBL的存在。该生物库与马约诊所的医疗记录相关联， 良好注释的前瞻性随访，以评价临床结局。生物银行的参与者还提供了 关于采血时流行病学、健康和行为风险因素的详细信息， 允许评估这些因素与MBL风险的关系。在本提案中，我们将利用这一独特的平台 明确与LC MBL相关的临床结局和发展该年龄的风险因素 相关的临床状况，影响5-10%的40岁以上的成年人。

Project Summary Our proposal addresses the important issue of defining the clinical consequences of low count Monoclonal B cell lymphocytosis (LC MBL) and providing insight into why 5-10% of U.S. adults over the age of 40 develop this condition. MBL - the precursor state to chronic lymphocytic leukemia (CLL), is one of the most common premalignant conditions in humans. Individuals with MBL have a circulating clonal B cell population, an absolute B cell count <5x109/L and no other features of a lymphoproliferative disorder. Studies have found that the prevalence of MBL increases with age, affecting <0.5% of individuals under age 40, 5% of those age 40-60, and over 10% of those over age 60. MBL is now subdivided into low count (LC) MBL and high count (HC) MBL depending on whether the absolute B cell count is above or below 1x109/L. The overwhelming majority (i.e. >98%) of individuals with MBL have LC MBL and never come to clinical attention. The clinical consequences of LC MBL are largely unknown. Despite the low risk of progression to CLL, individuals with LC MBL are likely to have other important clinical consequences. In a preliminary study of 1001 adults age >40, we found that individuals with LC MBL have reduced overall survival and increased risk of life-threatening infections. This suggests that 5-10% of adults over age 40 have a largely unstudied, acquired, asymptomatic condition with potentially important clinical implications. Currently little to no information is known about the risk factors for developing MBL. We are now poised via this proposal to determine the critical clinical consequences of LC MBL with respect to risk of infection and non-hematologic malignancy and to identify the risk factors for developing LC MBL. This is because of our unique opportunity to study MBL using the Mayo Clinic Biobank, the only tissue repository in the USA we are aware of that stores peripheral blood mononuclear cells in a manner that permits testing for the presence of LC MBL. This Biobank is linked to the Mayo Clinic Medical record and provides exceptionally well annotated prospective follow-up to evaluate clinical outcomes. Participants in the Biobank also provided detailed information on epidemiologic, health and behavioral risk factors at the time of blood collection which allows evaluation of how these factors relate to MBL risk. In this proposal, we will harness this unique platform to robustly define the clinical outcomes associated with LC MBL and the risk factors for developing this age related clinical condition which affects 5-10% of adults over the age of 40.