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抗B的临床后果这一重要问题 细胞淋巴细胞增多症(LC MBL)，并深入了解为什么40岁以上的美国成年人中有5%-10%的人会患上 这种情况。 MBL是慢性淋巴细胞白血病(CLL)的前驱状态，是最常见的癌前病变之一 人类的状况。患有MBL的人有循环中的克隆性B细胞群，绝对B细胞计数 &lt；5x109/L，没有淋巴增生性疾病的其他特征。研究发现，糖尿病的患病率 MBL随着年龄的增长而增加，40岁以下的人影响0.5%，40-60岁的人影响5%，超过10%的人 60岁以上的人。MBL现在细分为低计数(LC)MBL和高计数(HC)MBL，具体取决于 绝对B细胞计数是否高于或低于1x109/L。绝大多数(即98%) 患有MBL的患者患有LC MBL，并且从未引起临床注意。LC MBL的临床后果 在很大程度上是未知的。尽管进展到CLL的风险很低，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40岁成年人的初步研究中，我们发现患有LC MBL的个体总体上减少了 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种 很大程度上未被研究，获得性，无症状，具有潜在的重要临床意义。目前 关于发生MBL的风险因素，我们知之甚少甚至一无所知。我们现在准备好通过这一点 关于确定LC MBL相对于感染风险的严重临床后果的建议 和非血液系统恶性肿瘤，并找出发生LC MBL的危险因素。这是 因为我们有独特的机会使用Mayo Clinic Biobank研究MBL，这是美国唯一的组织信息库 我们所知道的美国以允许检测的方式存储外周血单核细胞 LC MBL的存在。这个生物库与梅奥诊所的医疗记录相关联，并提供了 有良好注解的前瞻性随访以评估临床结果。生物库的参与者还提供了 在采集血液时的流行病学、健康和行为危险因素的详细信息 允许评估这些因素与MBL风险的关系。在这项提议中，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到这个年龄段的危险因素 相关的临床症状，影响5-10%的40岁以上成年人。

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.