Department of Hematopathology Laboratory, ACTREC, Tata Memorial Center, HBNI University, Navi Mumbai, India.
Department of Department of Cancer Cytogenetics, ACTREC, Tata Memorial Center, HBNI University, Navi Mumbai, India.
Int J Lab Hematol. 2021 Oct;43(5):990-999. doi: 10.1111/ijlh.13456. Epub 2021 Jan 12.
Many new markers are being evaluated to increase the sensitivity and applicability of multicolor flow cytometry (MFC)-based measurable residual disease (MRD) monitoring. However, most of the studies are limited to childhood B-cell lymphoblastic leukemia/lymphoma (B-ALL), and reports in adult B-ALL are extremely scarce and limited to small cohorts. We studied the expression of CD304/neuropilin-1 in a large cohort of adult B-ALL patients and evaluated its practical utility in MFC-based MRD analysis.
CD304 was studied in blasts from adult B-ALL patients and normal precursor B cells (NPBC) from non-B-ALL bone marrow samples using MFC. CD304 expression intensity and pattern were studied with normalized-mean fluorescent intensity (nMFI) and coefficient of variation of immunofluorescence (CVIF), respectively. MFC-based MRD was performed at end of induction (EOI; day-35), end of consolidation (EOC; day 78-80), and subsequent follow-up (SFU) time points.
CD304 was positive in 120/214(56.07%) and was significantly associated with BCR-ABL1 fusion (P = .001). EOI-MRD and EOC-MRD were positive in 129/214(60.3%) and 50/81(61.72%), respectively. CD304 was positive in a significant percentage of EOI (48%, 62/129) and EOC (52%, 26/50) MRD-positive B-ALL samples. Its expression was retained, lost, and gained in 73.7%, 26.3%, and 11.3% of EOI-MRD and 85.7%, 14.3%, and none of EOC-MRD samples, respectively. Low-level MRD (<0.01%) was detectable in 34 of all (EOI + EOC + SFU = 189) MRD-positive samples, and CD304 was found useful in 50% of these samples.
CD304 is commonly expressed in adult B-ALL and clearly distinguish B-ALL blasts from normal precursor B cells. It is a stable MRD marker and distinctly useful in the detection of MFC-based MRD monitoring, especially in high-sensitivity MRD assay.
为了提高多色流式细胞术（MFC）基于残留疾病（MRD）监测的灵敏度和适用性，许多新的标志物正在被评估。然而，大多数研究仅限于儿童 B 细胞急性淋巴细胞白血病/淋巴瘤（B-ALL），并且成人 B-ALL 的报告极为罕见，仅限于小队列。我们研究了 CD304/神经纤毛蛋白-1 在一大群成人 B-ALL 患者中的表达，并评估了其在基于 MFC 的 MRD 分析中的实际应用。
使用 MFC 研究了成人 B-ALL 患者的白血病细胞和非 B-ALL 骨髓样本中的正常前体 B 细胞（NPBC）中的 CD304 表达。使用归一化平均荧光强度（nMFI）和免疫荧光变异系数（CVIF）分别研究 CD304 表达强度和模式。在诱导结束（EOI；第 35 天）、巩固结束（EOC；第 78-80 天）和随后的随访（SFU）时间点进行基于 MFC 的 MRD。
在 214 例中的 120 例（56.07%）中 CD304 呈阳性，与 BCR-ABL1 融合显著相关（P =.001）。EOI-MRD 和 EOC-MRD 分别在 129/214（60.3%）和 50/81（61.72%）例中为阳性。CD304 在 EOI（48%，62/129）和 EOC（52%，26/50）MRD 阳性的 B-ALL 样本中呈阳性的比例较高。其表达在 EOI-MRD 样本中的 73.7%（62/84）、26.3%（21/80）和 11.3%（9/76）中得到保留、丢失和获得，在 EOC-MRD 样本中的 85.7%（42/49）、14.3%（7/49）和 0%（0/51）中得到保留、丢失和获得。在所有（EOI+EOC+SFU=189）MRD 阳性样本中，有 34 个样本可检测到低水平的 MRD（<0.01%），而 CD304 在其中 50%的样本中有用。
CD304 在成人 B-ALL 中普遍表达，可清楚地区分 B-ALL 白血病细胞和正常前体 B 细胞。它是一种稳定的 MRD 标志物，在基于 MFC 的 MRD 监测中特别在高灵敏度的 MRD 检测中具有明显的作用。
