Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
Department of Pediatrics, National University of Singapore, Singapore.
J Formos Med Assoc. 2017 Oct;116(10):774-781. doi: 10.1016/j.jfma.2016.12.002. Epub 2017 Jan 4.
BACKGROUND/PURPOSE: Real-time quantitative polymerase chain reaction (RQ-PCR) for fusion transcripts and flow cytometry for leukemia-specific markers are widely used for minimal residual disease (MRD) detection in acute lymphoblastic leukemia, but the relation between the results of either method is unclear.
Mononucleated cells from 108 bone marrow samples collected from 55 B-precursor acute lymphoblastic leukemia patients (30 with t(12;21)/ETV6-RUNX1, 16 with t(9;22)/BCR-ABL1 and nine with t(1;19)/TCF3-PBX1) were examined in tandem by RQ-PCR and six-color flow cytometry.
MRD results were concordant in 91 of the 108 paired samples (84.2%; K=0.690); 49 samples were MRD-negative while 42 were MRD-positive by both methods, with < 1 log difference in positive MRD estimates in 39 samples (92.9%). Of the 17 discordant samples, 16 were MRD-positive by RQ-PCR but MRD-negative by flow cytometry; the opposite was true in one sample. Kappa value/concordance was 0.690/85.0% (n = 60) for ETV6-RUNX1, 0.842/93.3% (n = 15) for TCF3-PBX1, and 0.535/78.8% (n = 33) for BCR-ABL1. Specific immunophenotypic abnormalities were more prevalent in each genetic subgroup, such as CD38 underexpression, CD58 overexpression, and CD34 overexpression in ETV6-RUNX1, TCF3-PBX1, and BCR-ABL1, respectively.
In most follow-up samples, MRD estimates by two methods are in agreement, especially in patients with TCF3-PBX1.
背景/目的：实时定量聚合酶链反应（RQ-PCR）用于融合转录本和流式细胞术用于白血病特异性标志物，广泛用于急性淋巴细胞白血病的微小残留病（MRD）检测，但两种方法的结果之间的关系尚不清楚。
对 55 例 B 前体急性淋巴细胞白血病患者（30 例 t(12;21)/ETV6-RUNX1，16 例 t(9;22)/BCR-ABL1，9 例 t(1;19)/TCF3-PBX1）的 108 个骨髓样本的单核细胞进行了 RQ-PCR 和六色流式细胞术的串联检测。
在 108 对配对样本中的 91 对（84.2%；K=0.690）MRD 结果一致；49 个样本为 MRD 阴性，而两种方法均为 MRD 阳性，39 个样本（92.9%）的阳性 MRD 估计值相差<1 个对数级。在 17 个不一致的样本中，16 个样本 RQ-PCR 为 MRD 阳性，但流式细胞术为 MRD 阴性；一个样本则相反。对于 ETV6-RUNX1，Kappa 值/一致性为 0.690/85.0%（n=60），对于 TCF3-PBX1，为 0.842/93.3%（n=15），对于 BCR-ABL1，为 0.535/78.8%（n=33）。每种遗传亚组中更常见特定免疫表型异常，例如 ETV6-RUNX1 中 CD38 表达不足，TCF3-PBX1 中 CD58 过度表达，BCR-ABL1 中 CD34 过度表达。
在大多数随访样本中，两种方法的 MRD 估计值是一致的，尤其是在 TCF3-PBX1 患者中。
