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在B细胞前体急性淋巴细胞白血病患者缓解诱导治疗阶段监测微小残留病时异常标志物的表达

Expression of aberrant markers in monitoring of measurable residual disease in B-cell precursor acute lymphoblastic leukemia patients during remission-inducing therapy phase.

作者信息

Słota Ł, Sędek Ł, Lejman M, Perkowski B, Lasia A, Bulsa J, Młynarski W, Kowalczyk J, Szczepański T

机构信息

Department of Pediatric Hematology and Oncology, Medical University of Silesia, Katowice, Poland.

Department of Microbiology and Immunology, Medical University of Silesia, Katowice, Poland.

出版信息

Front Oncol. 2025 Aug 27;15:1641088. doi: 10.3389/fonc.2025.1641088. eCollection 2025.

Abstract

INTRODUCTION

B-cell acute lymphoblastic leukemia (BCP-ALL) is characterized by an abnormal proliferation of immature cells in bone marrow. Leukemic blasts at diagnosis exhibit a so-called leukemia associated immunophenotype (LAIP), which is further used for determination of measurable residual disease (MRD) levels at particular time points during the therapy. Nevertheless, in some patients LAIP proves insufficient for discrimination of blasts from their normal counterparts, therefore, search for novel, aberrant markers is essential. A crucial requirement for these antigens is their expression variability throughout the entire treatment monitoring period.

METHODS

The aim of the study was to assess the expression level of four markers: CD66c, CD304, CD72 and CD86 on leukemic cells at diagnosis and at day 15 and 33 of treatment to compare stability of their expression. We also correlated the results obtained with the most common genetic aberrations identified at the diagnosis of BCP-ALL, such as: hyper- hypodiploidy, , , , , , , and mutations.

RESULTS

In more than 90% of patients, CD86 overexpression on blast cells was proven at day 15 of treatment and in almost 93% during the entire remission-inducting therapy (day 33). Similarly high positivity rate on leukemic blasts was found for CD72 antigen, which at day 15 was positive in 82% of patients and dropped to 43% at day 33 of treatment. We also found a correlation between the presence of hyperdiploidy and and changes in the expression of particular markers.

DISCUSSION

The obtained results demonstrate that CD86 and CD72 can be successfully used as additional markers for MRD assessment in BCP-ALL.

摘要

引言

B细胞急性淋巴细胞白血病(BCP-ALL)的特征是骨髓中未成熟细胞异常增殖。诊断时的白血病原始细胞表现出所谓的白血病相关免疫表型(LAIP),该表型进一步用于确定治疗期间特定时间点的可测量残留病(MRD)水平。然而,在一些患者中,LAIP被证明不足以区分原始细胞与其正常对应物,因此,寻找新的异常标志物至关重要。这些抗原的一个关键要求是它们在整个治疗监测期内的表达变异性。

方法

本研究的目的是评估四种标志物:CD66c、CD304、CD72和CD86在诊断时以及治疗第15天和第33天白血病细胞上的表达水平,以比较它们表达的稳定性。我们还将获得的结果与BCP-ALL诊断时确定的最常见基因异常相关联,例如:超二倍体、 、 、 、 、 、 以及 突变。

结果

在超过90%的患者中,治疗第15天证实原始细胞上存在CD86过表达,在整个诱导缓解治疗期间(第33天)几乎为93%。CD72抗原在白血病原始细胞上也有同样高的阳性率,在第15天82%的患者呈阳性,在治疗第33天降至43%。我们还发现超二倍体的存在与特定标志物表达的变化之间存在相关性。

讨论

获得的结果表明,CD86和CD72可成功用作BCP-ALL中MRD评估的额外标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff5e/12420255/1528b38f1af4/fonc-15-1641088-g001.jpg

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