Rawstron Andy C, Ssemaganda Aloysius, de Tute Ruth, Doughty Chi, Newton Darren, Vardi Anna, Evans Paul A S, Stamatopoulos Kostas, Owen Roger G, Lightfoot Tracy, Wakeham Katie, Karabarinde Alex, Asiki Gershim, Newton Robert
Haematological Malignancy Diagnostic Service, St James's University Hospital, Leeds, UK.
International AIDS Vaccine Initiative, Uganda Virus Research Institute, Entebbe, Uganda.
Lancet Haematol. 2017 Jul;4(7):e334-e340. doi: 10.1016/S2352-3026(16)30192-2.
Reported incidence of B-cell malignancies shows substantial geographical variation, being more common in the Americas and Europe than in Africa. This variation might reflect differences in diagnostic capability, inherited susceptibility, and infectious exposures. Monoclonal B-cell lymphocytosis (MBL) is a precursor lesion that can be screened for in apparently healthy people, allowing comparison of prevalence across different populations independently of health-care provision. We aimed to compare the prevalence and phenotypic characteristics of MBL in age-and-sex-matched populations from rural Uganda and the UK.
In this cross-sectional study, we recruited volunteers aged at least 45 years who were seronegative for HIV-1 from the established Ugandan General Population Cohort and obtained their whole-blood samples. We also obtained blood samples from anonymised waste material of age-and-sex-matched individuals (aged >45 years, with a normal blood count and no history of cancer) in the UK. We used flow cytometry to determine the presence of MBL, defined according to standard diagnostic criteria, in the samples and compared differences in the proportion of cases with chronic lymphocytic leukaemia (CLL)-phenotype MBL and CD5-negative MBL, as well as differences in absolute monoclonal B-cell count between the two cohorts.
Between Jan 15 and Dec 18, 2012, we obtained samples from 302 Ugandan volunteers and 302 UK individuals who were matched by age and sex to the Ugandan population. Overall MBL prevalence was higher in the Ugandan participants (42 [14%] individuals) than in the UK cohort (25 [8%]; p=0·038). CLL-phenotype MBL was detected in three (1%) Ugandan participants and 21 (7%) UK participants (p=0·00021); all three Ugandan participants had absolute monoclonal B-cell count below one cell per μL, whereas the 21 UK participants had a median absolute number of circulating neoplastic cells of 4·6 (IQR 2-12) cells per μL. The prevalence of CD5-negative MBL was higher in the Ugandan cohort (41 [14%], of whom two [5%] also had CLL-phenotype MBL) than in the UK cohort (six [2%], of whom two [33%] also had CLL-phenotype MBL; p<0·0001), but the median absolute B-cell count was similar (227 [IQR 152-345] cells per μL in the Ugandan cohort vs 135 [105-177] cells per μL in the UK cohort; p=0·13).
MBL is common in both Uganda and the UK, but the substantial phenotypic differences might reflect fundamental differences in the pathogenesis of B-cell lymphoproliferative disorders.
UK Medical Research Council and UK Department for International Development.
据报道，B 细胞恶性肿瘤的发病率存在显著的地域差异，在美洲和欧洲比在非洲更为常见。这种差异可能反映了诊断能力、遗传易感性和感染暴露方面的差异。单克隆 B 淋巴细胞增多症（MBL）是一种前驱病变，可在看似健康的人群中进行筛查，从而能够独立于医疗保健服务情况来比较不同人群中的患病率。我们旨在比较来自乌干达农村和英国的年龄及性别匹配人群中 MBL 的患病率和表型特征。
在这项横断面研究中，我们从已建立的乌干达普通人群队列中招募了年龄至少 45 岁且 HIV-1 血清学阴性的志愿者，并获取他们的全血样本。我们还从英国年龄及性别匹配个体（年龄>45 岁，血细胞计数正常且无癌症病史）的匿名废弃材料中获取血样。我们使用流式细胞术来确定样本中是否存在根据标准诊断标准定义的 MBL，并比较慢性淋巴细胞白血病（CLL）表型 MBL 和 CD5 阴性 MBL 病例比例的差异，以及两个队列之间绝对单克隆 B 细胞计数的差异。
在 2012 年 1 月 15 日至 12 月 18 日期间，我们从 302 名乌干达志愿者和 302 名与乌干达人群年龄和性别匹配的英国个体中获取了样本。乌干达参与者中 MBL 的总体患病率（42 人[14%]）高于英国队列（25 人[8%]；p = 0·038）。在 3 名（1%）乌干达参与者和 21 名（7%）英国参与者中检测到 CLL 表型 MBL（p = 0·00021）；所有 3 名乌干达参与者的绝对单克隆 B 细胞计数低于每微升 1 个细胞，而 21 名英国参与者循环肿瘤细胞的中位数绝对数量为每微升 4·6（IQR 2 - 12）个细胞。乌干达队列中 CD5 阴性 MBL 的患病率（41 人[‘14%’]，其中 2 人[5%]也有 CLL 表型 MBL）高于英国队列（6 人[2%]，其中 2 人[33%]也有 CLL 表型 MBL；p<0·0001），但中位数绝对 B 细胞计数相似（乌干达队列中为每微升 227（IQR 152 - 345）个细胞，英国队列中为每微升 135（105 - 177）个细胞；p = 0·13）。
MBL 在乌干达和英国都很常见，但显著的表型差异可能反映了 B 细胞淋巴增殖性疾病发病机制的根本差异。
英国医学研究理事会和英国国际发展部。
