DiGiuseppe Joseph A, Tadmor Michelle D, Pe'er Dana
Department of Pathology & Laboratory Medicine, Hartford Hospital, Hartford, Connecticut.
Department of Biological Sciences, Columbia University, New York, New York.
Cytometry B Clin Cytom. 2015 Sep-Oct;88(5):294-304. doi: 10.1002/cyto.b.21252. Epub 2015 Jun 2.
Minimal residual disease (MRD) following treatment is a robust prognostic marker in B lymphoblastic leukemia. However, the detection of MRD by flow cytometric immunophenotyping is technically challenging, and an automated method to detect MRD is therefore desirable. viSNE, a recently developed computational tool based on the t-Distributed Stochastic Neighbor Embedding (t-SNE) algorithm, has been shown to be capable of detecting synthetic "MRD-like" populations of leukemic cells created in vitro, but whether viSNE can facilitate the immunophenotypic detection of MRD in clinical samples has not been evaluated.
We applied viSNE retrospectively to 8-color flow cytometric immunophenotyping data from normal bone marrow samples, and samples from B lymphoblastic leukemia patients with or without suspected MRD on the basis of conventional manual gating.
In each of 14 bone marrow specimens containing MRD or suspected MRD, viSNE identified a putative MRD population; an abnormal composite immunophenotype was confirmed for the putative MRD in each case. MRD populations were not identified by viSNE in control bone marrow samples from patients with increased normal B-cell precursors, or in post-treatment samples from B lymphoblastic leukemia patients who did not have detectable MRD by manual gating.
viSNE shows promise as an automated method to facilitate immunophenotypic MRD detection in patients treated for B lymphoblastic leukemia.
治疗后的微小残留病（MRD）是B淋巴细胞白血病中一种可靠的预后标志物。然而，通过流式细胞术免疫表型分析检测MRD在技术上具有挑战性，因此需要一种自动化的方法来检测MRD。viSNE是一种最近基于t分布随机邻域嵌入（t-SNE）算法开发的计算工具，已被证明能够检测体外创建的白血病细胞的合成“MRD样”群体，但viSNE是否能促进临床样本中MRD的免疫表型检测尚未得到评估。
我们回顾性地将viSNE应用于正常骨髓样本以及基于传统手工设门法判断有或无疑似MRD的B淋巴细胞白血病患者样本的8色流式细胞术免疫表型分析数据。
在14个含有MRD或疑似MRD的骨髓标本中，viSNE均识别出一个假定的MRD群体；在每种情况下，均证实该假定的MRD具有异常的复合免疫表型。在正常B细胞前体增加的患者的对照骨髓样本中，或在经手工设门法未检测到MRD的B淋巴细胞白血病患者的治疗后样本中，viSNE未识别出MRD群体。
viSNE作为一种自动化方法，有望促进接受B淋巴细胞白血病治疗患者的免疫表型MRD检测。
