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在针对 CD19 后,B 细胞前体急性淋巴细胞白血病微小残留病监测中有用的 B 谱系抗原可替代 CD19。

B-lineage antigens that are useful to substitute CD19 for minimal residual disease monitoring in B cell precursor acute lymphoblastic leukemia after CD19 targeting.

机构信息

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation.

出版信息

Cytometry B Clin Cytom. 2022 Sep;102(5):353-359. doi: 10.1002/cyto.b.22088. Epub 2022 Jul 7.

Abstract

BACKGROUND

The potential loss of CD19 during targeted treatment of B cell precursor acute lymphoblastic leukemia (BCP-ALL) can hamper flow cytometric minimal residual disease (MRD) monitoring. In the current study, we present expression data for antigens that are candidates for CD19 substitution: surface CD22, CD24, CD10, and intracellular (i) CD79a.

METHODS

Bone marrow samples from 519 consecutive children (below 18 y.o.) with primary BCP-ALL were studied with a focus on expression of CD19, CD10, CD22, CD24, and iCD79a. As these antigens are planned to be used as substitutions for CD19 for primary B cell gating, only total expression on the leukemic population (≥95% cells) was considered appropriate.

RESULTS

It was found that each of these antigens is totally expressed in nearly 90% of patients. For each single marker, a subgroup of patients without complete positivity presented with BCP-ALL harboring diverse cytogenetic and molecular genetic aberrations. Based on expression data, we have developed algorithm of simultaneous application of these antigens for initial B-lineage compartment gating, that is applicable for nearly all patients after CD19 targeting.

CONCLUSION

We conclude that the addition of CD22, CD24, and iCD79a to the conventional antibody panel and their application together with CD10 allow for the identification of B-lineage compartment including residual tumor blasts, for MFC-MRD searching in virtually all patients with BCP-ALL after CD19-directed treatment.

摘要

背景

在靶向治疗 B 细胞前体急性淋巴细胞白血病(BCP-ALL)的过程中,CD19 的潜在丢失可能会阻碍流式细胞术微小残留病(MRD)监测。在本研究中,我们提供了候选替代 CD19 的抗原的表达数据:表面 CD22、CD24、CD10 和细胞内(i)CD79a。

方法

对 519 例原发性 BCP-ALL 儿童(<18 岁)的骨髓样本进行研究,重点关注 CD19、CD10、CD22、CD24 和 iCD79a 的表达。由于这些抗原计划用于替代 CD19 进行原发性 B 细胞门控,因此仅考虑在白血病群体(≥95%的细胞)上的总表达是合适的。

结果

发现这些抗原中的每一种在近 90%的患者中均完全表达。对于每个单一标志物,都存在一个亚组患者不完全阳性,这些患者具有不同的细胞遗传学和分子遗传学异常。基于表达数据,我们开发了同时应用这些抗原进行初始 B 细胞谱系门控的算法,该算法几乎适用于所有经 CD19 靶向治疗后的患者。

结论

我们得出结论,将 CD22、CD24 和 iCD79a 添加到常规抗体组合中,并将其与 CD10 一起应用,可以识别包括残留肿瘤细胞的 B 细胞谱系,用于几乎所有接受 CD19 定向治疗后的 BCP-ALL 患者的 MFC-MRD 搜索。

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