In this study, we aimed to identify patients within our B-ALL cohort with alteredPAX5. Our objective was to use a comprehensive analysis approach to characterize the types of genetic changes, determine their origin (somatic/germline), and analyze the clinical outcomes associated with them. A consecutive cohort of 99 patients with B-ALL treated at the Children’s Hospital of the UMC Ljubljana according to the ALL IC-BFM 2009 protocol was included in our study. We used RNA sequencing data for gene expression analysis, fusion gene detection and single nucleotide variant identification, multiplex-ligation dependent probe amplification for copy number variation assessment, and Sanger sequencing for germline variant detection.PAX5was impacted in 33.3% of our patients, with the genetic alterations ranging from CNVs and rearrangements to SNVs. The most common were CNVs, which were found in more than a third of patients, followed by point mutations in 5.2%, and gene rearrangements in 4.1%. We identified eight patients with aPAX5-associated genetic subtype that were previously classified as “B-other”, and they showed intermediate outcomes. We showed higher minimal residual disease values at the end of induction and poorer event-free survival in hyperdiploid cases carrying duplications inPAX5compared to other hyperdiploid cases. We also report an interesting case of a patient withPAX5::FKBP15and a pathogenic variant inPTPN11who underwent an early relapse with a monocytic switch. In conclusion, this study provides valuable insights into the presence, frequency, and prognostic significance of diversePAX5alterations in B-ALL patients, highlighting the complexity of genetic factors and their impact on patient outcomes.
本研究旨在从B细胞急性淋巴细胞白血病（B-ALL）队列中筛选存在PAX5基因异常的患者，通过综合分析明确基因改变类型、判定其起源（体细胞/胚系），并探讨其与临床结局的关联。研究连续纳入99例在卢布尔雅那大学医学中心儿童医院接受ALL IC-BFM 2009方案治疗的B-ALL患者，采用RNA测序数据进行基因表达分析、融合基因检测及单核苷酸变异鉴定，多重连接探针扩增技术进行拷贝数变异评估，Sanger测序检测胚系变异。结果显示33.3%的患者存在PAX5基因异常，包括拷贝数变异、基因重排及单核苷酸变异等多种形式。其中拷贝数变异最为常见（超过三分之一患者），点突变（5.2%）和基因重排（4.1%）次之。研究新发现8例携带PAX5相关遗传亚型的患者（原分类为“B-其他”型），其临床结局呈中等风险特征。与其它高超二倍体病例相比，携带PAX5重复变异的高超二倍体患者在诱导治疗结束时的微小残留病水平更高，无事件生存率更差。此外，研究报道一例同时存在PAX5::FKBP15融合基因与PTPN11致病性变异的特殊病例，该患者早期复发并伴随单核细胞系转换。本研究系统揭示了B-ALL患者中PAX5基因异常的多样性、发生频率及其预后意义，强调了遗传因素的复杂性及其对临床结局的重要影响。
肿瘤(癌症)患者之家