High-Dimensional Analysis of Acute Myeloid Leukemia Reveals Phenotypic Changes in Persistent Cells during Induction Therapy.
High-Dimensional Analysis of Acute Myeloid Leukemia Reveals Phenotypic Changes in Persistent Cells during Induction Therapy.
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DOI：
10.1371/journal.pone.0153207
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Irish JM
中科院分区：
文献类型：
--
作者：
Ferrell PB Jr;Diggins KE;Polikowsky HG;Mohan SR;Seegmiller AC;Irish JM
AML的可塑性导致临床结果不佳，并混淆了其纵向检测。然而，治疗对骨髓和血液中白血病和非白血病细胞的直接影响仍然相对研究不足。在这里，我们进行了一项试点研究，在AML的免疫表型的高维纵向监测。为了表征诱导治疗之前、期间和之后立即发生的细胞表型变化，我们开发了一种27抗体组，用于集中于表面诊断标记物的质谱细胞术，并将其应用于随时间从5名AML患者收集的46份血液或骨髓组织样本。中心目标是确定AML表型的变化是否会被细胞组学工具有效捕获，并实施用于描述AML细胞亚群的演变表型的方法。使用已建立的计算技术分析质谱细胞术数据。在这项初步研究中，采用质谱细胞术进行的纵向免疫监测揭示了在难治性疾病背景下诱导期间和诱导后随时间推移发生的白血病表型的根本变化。持续存在的AML原始细胞在表型上与干细胞和祖细胞更加不同，这是由于表达了与治疗前AML细胞和健康骨髓中观察到的所有细胞类型不同的新型标志物模式。这项AML单细胞免疫监测的初步研究代表了精确表征和靶向耐药疾病的强大工具。
The plasticity of AML drives poor clinical outcomes and confounds its longitudinal detection. However, the immediate impact of treatment on the leukemic and non-leukemic cells of the bone marrow and blood remains relatively understudied. Here, we conducted a pilot study of high dimensional longitudinal monitoring of immunophenotype in AML. To characterize changes in cell phenotype before, during, and immediately after induction treatment, we developed a 27-antibody panel for mass cytometry focused on surface diagnostic markers and applied it to 46 samples of blood or bone marrow tissue collected over time from 5 AML patients. Central goals were to determine whether changes in AML phenotype would be captured effectively by cytomic tools and to implement methods for describing the evolving phenotypes of AML cell subsets. Mass cytometry data were analyzed using established computational techniques. Within this pilot study, longitudinal immune monitoring with mass cytometry revealed fundamental changes in leukemia phenotypes that occurred over time during and after induction in the refractory disease setting. Persisting AML blasts became more phenotypically distinct from stem and progenitor cells due to expression of novel marker patterns that differed from pre-treatment AML cells and from all cell types observed in healthy bone marrow. This pilot study of single cell immune monitoring in AML represents a powerful tool for precision characterization and targeting of resistant disease.