PDF(Pubmed)
Abstract：
In recent years, the significance of detecting minimal/measurable residual disease (MRD) in chronic lymphocytic leukemia (CLL) has increased due to the availability of highly effective therapeutic agents. Flow cytometry provides notable cost-effectiveness and immediacy, with an expected sensitivity level of approximately 10-4. The critical aspect of MRD detection via flow cytometry lies in accurately defining the region containing tumor cells. However, a subset of CLL, known as CLL with atypical immunophenotype, exhibits a distinct cell surface marker expression pattern that can make MRD detection challenging, because these markers often resemble those of normal B cells. To enhance the sensitivity of MRD detection in such atypical cases of CLL, we have capitalized on the observation that cell surface immunoglobulin (sIg) light chains tend to be expressed at a higher level in this subtype. For every four two-dimensional plots of cell surface markers, we used a plot to evaluate the expression of sIg kappa/lambda light chains and identified regions where the kappa/lambda ratio of sIg light chains deviated from a designated threshold within the putative CLL cell region. Using this method, we could detect atypical CLL cells at a level of 10-4. We propose this method as an effective MRD assay.
摘要：
近年来,在慢性淋巴细胞白血病(CLL)中检测微小/可测量的残留病(MRD)的重要性由于高效治疗药物的可用性而增加.流式细胞术提供了显着的成本效益和即时性，预期灵敏度水平约为10-4。通过流式细胞术检测MRD的关键方面在于准确定义含有肿瘤细胞的区域。然而,CLL的一个子集，称为具有非典型免疫表型的CLL，表现出独特的细胞表面标记表达模式，可以使MRD检测具有挑战性，因为这些标记通常与正常B细胞相似。为了提高MRD在此类非典型CLL病例中检测的灵敏度，我们利用了细胞表面免疫球蛋白(sIg)轻链在该亚型中倾向于以更高的水平表达的观察结果。对于每四个细胞表面标记的二维图，我们使用曲线图评估sIgκ/λ轻链的表达,并确定了sIg轻链的κ/λ比值偏离假定CLL细胞区域内指定阈值的区域.使用此方法，我们可以检测到10-4水平的非典型CLL细胞。我们提出这种方法作为一种有效的MRD检测方法。
