Hematopathology Laboratory, ACTREC, Tata Memorial Center, HBNI University, Navi Mumbai, India.
Homi Bhabha National Institute, Mumbai, Maharashtra.
Cytometry B Clin Cytom. 2020 Jul;98(4):328-335. doi: 10.1002/cyto.b.21866. Epub 2020 Jan 16.
Measurable residual disease (MRD) assessment using multicolor flow cytometry (MFC) has become the center point of pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) risk stratification and therapeutic management. The addition of new markers can improve the accuracy and applicability of MFC-based MRD assay further. Herein, we evaluated the utility of a new marker, CD304/neuropilin-1, in the assessment of MFC-based MRD.
Expression patterns of CD304 were studied in leukemic blasts from BCP-ALL patients and in normal precursor B cells (NPBC) from uninvolved non-BCP-ALL bone marrow samples using 10-color MFC. MRD was monitored at end-of-induction (EOI; Days 35-40) and end-of-consolidation (Day 78-80) time points.
We studied CD304 expression in 300 pediatric BCP-ALL patients and found it positive in BCP-ALL blasts in 41.7% of diagnostic samples. It was significantly associated with ETV6-RUNX1 (p < .001) as well as BCR-ABL1 (p = .019) and inversely associated with TCF3-PBX1 fusion gene (p = .0012). It was found clearly negative in NPBC. EOI-MRD was detectable in 152/300 (50.7%; ≥0.01% in 35.33% and <0.01% in 15.33%) samples, in which CD304 was positive in 72/152 (47.4%) diagnostic and 63/152 (41.4%) MRD samples. It was positive in 45.7% (21/46) of low-level (<0.01%) MRD samples. In comparison with diagnostic samples, its expression was retained in 68.06% (49/72), lost in 31.94% (23/72), and gained in 14/80 (17.5%) of EOI-MRD samples.
CD304 is commonly expressed in leukemic blasts of BCP-ALL. It is very useful in distinguishing residual disease from hematogones and is a fairly dependable marker. Hence, it is a valuable addition for enhancing the sensitivity and applicability of MFC-based MRD assay in BCP-ALL.
使用多色流式细胞术（MFC）进行可测量残留疾病（MRD）评估已成为小儿 B 细胞前体急性淋巴细胞白血病（BCP-ALL）风险分层和治疗管理的重点。添加新的标志物可以进一步提高基于 MFC 的 MRD 检测的准确性和适用性。在此，我们评估了一种新标志物 CD304/神经纤毛蛋白-1 在基于 MFC 的 MRD 评估中的应用价值。
使用 10 色 MFC 研究了 BCP-ALL 患者白血病blasts 中 CD304 的表达模式，并研究了未受累非 BCP-ALL 骨髓样本中正常前体 B 细胞（NPBC）中的 CD304 表达模式。在诱导结束（EOI；第 35-40 天）和巩固结束（第 78-80 天）时间点监测 MRD。
我们研究了 300 例小儿 BCP-ALL 患者的 CD304 表达，发现 41.7%的诊断样本中 BCP-ALLblasts 呈阳性。它与 ETV6-RUNX1（p<0.001）显著相关，与 BCR-ABL1（p=0.019）相关，与 TCF3-PBX1 融合基因（p=0.0012）呈负相关。在 NPBC 中它明显呈阴性。在 300 例患者中有 152 例（50.7%；35.33%的样本中有≥0.01%，15.33%的样本中有<0.01%）在 EOI 可检测到 MRD，其中 152 例中的 72 例（72/152）在诊断和 152 例中的 63 例（63/152）在 MRD 中呈阳性。在 45.7%（21/46）的低水平（<0.01%）MRD 样本中呈阳性。与诊断样本相比，其表达在 68.06%（49/72）的 EOI-MRD 样本中保持，在 31.94%（23/72）的样本中丢失，在 80 例中的 14 例（17.5%）的样本中获得（80/80）。
CD304 在 BCP-ALL 的白血病blasts 中广泛表达。它在区分残留疾病与血原细胞方面非常有用，是一种相当可靠的标志物。因此，它是增强基于 MFC 的 BCP-ALL MRD 检测的敏感性和适用性的有价值的补充。
