Shires Karen, Wyk Teagan Van, Wienand Kirsty
Division of Haematology, Department of Pathology, University of Cape Town and National Health Laboratory Service/Groote Schuur Hospital, South Africa.
Department of Medicine, University of Cape Town, Cape Town, South Africa.
Blood Res. 2021 Sep 30;56(3):156-165. doi: 10.5045/br.2021.2020335.
It is thought that cancer/testis antigens (CTAs) are expressed in a cascade-like manner in multiple myeloma as the disease progresses. In this pilot study, we investigated the co-expression of several CTAs in the peripheral blood (PB) during patient therapy to establish whether monitoring multiple CTAs allows for the prediction of relapse and clonal evolution.
We examined the co-expression of , and via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) duplex assays in the PB mononuclear cells of 10 patients on chemotherapy at 3-month intervals, and correlated the levels to those of two basic clinical monitoring markers, serum -2-microglobulin and serum M protein. Clonal evolution was investigated using flow cytometry to label the circulating malignant stem cell components with MAGEC1, PRAME, and MAGEA3 antibodies.
Simultaneous monitoring of provided sensitive detection of circulating malignant cells in easily accessible PB samples; transcript levels increased prior to changes in indicators of clinical relapse. While expression levels did not offer earlier prediction of relapse, they provided insight into significant changes occurring within the malignant cell population; the addition of either CTA to a -monitoring panel allowed for better classification of the relapse event (clonal evolution), which in turn could potentially guide treatment strategies in the future.
This pilot study supports the novel idea of determining the levels and CTA expression patterns of the total circulating malignant cell population (pro-B/pre-B stem cell progenitors and proliferating plasma cells) as an alternate disease monitoring methodology.
人们认为，随着疾病进展，癌胚抗原（CTAs）在多发性骨髓瘤中以级联样方式表达。在这项初步研究中，我们调查了患者治疗期间外周血（PB）中几种CTAs的共表达情况，以确定监测多种CTAs是否有助于预测复发和克隆进化。
我们通过定量逆转录-聚合酶链反应（qRT-PCR）双链分析，每隔3个月检测10例接受化疗患者外周血单个核细胞中 、 和 的共表达情况，并将其水平与两种基本临床监测指标血清β-2微球蛋白和血清M蛋白的水平相关联。使用流式细胞术，用MAGEC1、PRAME和MAGEA3抗体标记循环恶性干细胞成分，研究克隆进化。
同时监测 可在易于获取的PB样本中灵敏检测循环恶性细胞；转录水平在临床复发指标变化之前升高。虽然 表达水平不能更早预测复发，但它们能深入了解恶性细胞群体内发生的显著变化；将任何一种CTA添加到 监测组中，都能更好地对复发事件（克隆进化）进行分类，这反过来可能会在未来指导治疗策略。
这项初步研究支持了一种新的观点，即确定总循环恶性细胞群体（前B/前B干细胞祖细胞和增殖浆细胞）的水平和CTA表达模式，作为一种替代的疾病监测方法。
