Pierzyna-Świtała Magdalena, Sędek Łukasz, Kulis Jan, Mazur Bogdan, Muszyńska-Rosłan Katarzyna, Kołtan Andrzej, Woszczyk Mariola, Niedźwiecki Maciej, Mizia-Malarz Agnieszka, Karolczyk Grażyna, Lejman Monika, Trelińska Joanna, Badowska Wanda, Derwich Katarzyna, Ociepa Tomasz, Malinowska Iwona, Kazanowska Bernarda, Kowalczyk Jerzy, Szczepański Tomasz
Department of Microbiology and Immunology, Medical University of Silesia, Zabrze, Poland.
Department of Pediatric Hematology and Oncology, Medical University of Silesia, Katowice, Poland.
Cent Eur J Immunol. 2021;46(3):365-374. doi: 10.5114/ceji.2021.109794. Epub 2021 Oct 19.
The aim of this study was to assess the incidence of DNA aneuploidy in Polish children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL) and the relationship between aneuploidy and immunological phenotype, age, leukocyte count, S-phase fraction (SPF) and early response to induction chemotherapy assessed by the percentage of residual blast cells in bone marrow aspirates. The study group consisted of 267 patients. DNA content and immunophenotype were assessed in the bone marrow before treatment using multicolor flow cytometry (FC). DNA aneuploidy was detected in 50/267 (19%) patients. High hyperdiploidy was found to be associated with lower leukocyte count (p = 0.006) and common ALL immunophenotype. Flow cytometry analysis revealed that high hyperdiploid BCP-ALL patients showed significantly higher expression of CD9, CD20, CD22, CD58, CD66c, CD86 and CD123 antigens as compared to other groups of ploidy. In contrast, CD45 showed decreased expression. The percentage of leukemic blasts at diagnosis was lower in high hyperdiploid BCP-ALL cases than in diploid (79% vs. 85.7%, p = 0.001). The difference in minimal residual disease (MRD) levels on day 15 and 33 of induction therapy between analyzed groups was not significant. This study showed that high hyperdiploidy is associated with lower WBC count and specific immunological phenotype. Flow cytometric evaluation of expression of selected antigens can be used for fast identification of markers of aneuploidy in pediatric BCP-ALL, before genetic tests results are available. Understanding the biological significance of aneuploidy in leukemia can potentially be exploited therapeutically using targeted therapies against specific blast cell subclones.
本研究旨在评估波兰B细胞前体急性淋巴细胞白血病（BCP-ALL）患儿中DNA非整倍体的发生率，以及非整倍体与免疫表型、年龄、白细胞计数、S期分数（SPF）和诱导化疗早期反应（通过骨髓穿刺液中残留原始细胞百分比评估）之间的关系。研究组由267名患者组成。治疗前使用多色流式细胞术（FC）评估骨髓中的DNA含量和免疫表型。在267例患者中有50例（19%）检测到DNA非整倍体。发现高超二倍体与较低的白细胞计数（p = 0.006）和常见ALL免疫表型相关。流式细胞术分析显示，与其他倍体组相比，高超二倍体BCP-ALL患者的CD9、CD20、CD22、CD58、CD66c、CD86和CD123抗原表达显著更高。相反，CD45表达降低。高超二倍体BCP-ALL病例诊断时白血病原始细胞百分比低于二倍体病例（79%对85.7%，p = 0.001）。分析组之间诱导治疗第15天和第33天的微小残留病（MRD）水平差异不显著。本研究表明，高超二倍体与较低的白细胞计数和特定免疫表型相关。在基因检测结果出来之前，对选定抗原表达进行流式细胞术评估可用于快速识别儿童BCP-ALL中非整倍体的标志物。了解白血病中非整倍体的生物学意义可能会通过针对特定原始细胞亚克隆的靶向治疗在治疗中得到利用。
