Background: In childhood acute lymphoblastic leukemia (ALL), in addition to classical chromosomal abnormalities, loss of heterozygosity (LOH), including copy-neutral LOH, is also observed. While LOH has been described in the literature, its clinical relevance in pediatric ALL remains unclear. The aim of this study is to identify and analyze patterns of LOH, assess their frequency, and evaluate their association with clinical characteristics and early treatment response during the induction phase of the ALL protocol. Methods: The study included 853 pediatric ALL patients, of whom 120 had B-ALL LOH+ and 58 had T-ALL LOH+. LOH was analyzed using CytoScan HD SNP microarrays. Patients were stratified using multiple correspondence analysis (MCA) and hierarchical clustering on principal components (HCPC), which identified three genetically and clinically distinct clusters. Results: In B-ALL, two clusters with extensive LOH—particularly involving chromosome 9—were associated with poor prognosis and suboptimal response to therapy. In contrast, Cluster 2, characterized by CDKN2A duplication and rare LOH, showed a favorable clinical course. In T-ALL, Cluster 1 had LOH in CDKN2A but favorable outcomes; Cluster 2 exhibited biallelic CDKN2A deletion and aggressive disease; Cluster 3 lacked CDKN2A alterations and showed a genetically stable profile. LOH was common on chromosomes not typically affected by trisomy and rare on those gained. Conclusions: Our study indicates that LOH profiling can positively influence patient stratification by identifying high-risk subgroups, inform prognosis by highlighting unfavorable genetic alterations, and help predict poor treatment response in specific clinical profiles.
背景：在儿童急性淋巴细胞白血病（ALL）中，除经典染色体异常外，杂合性缺失（包括拷贝中性LOH）也常被观察到。尽管文献中已有LOH的相关描述，但其在儿童ALL中的临床意义仍不明确。本研究旨在识别并分析LOH模式，评估其发生频率，并探究其与ALL方案诱导期临床特征及早期治疗反应的相关性。方法：研究纳入853例儿童ALL患者，其中120例为B-ALL LOH+，58例为T-ALL LOH+。采用CytoScan HD SNP芯片进行LOH分析。通过多重对应分析和主成分层次聚类对患者进行分层，识别出三个遗传学与临床特征各异的聚类群组。结果：在B-ALL中，两个存在广泛LOH（尤其涉及9号染色体）的聚类群组与不良预后及治疗反应欠佳相关。而具有CDKN2A重复和罕见LOH特征的聚类群组2则表现出良好的临床病程。在T-ALL中，聚类群组1虽存在CDKN2A的LOH但预后良好；聚类群组2表现为CDKN2A双等位基因缺失及侵袭性疾病特征；聚类群组3无CDKN2A改变且呈现遗传稳定特征。LOH常见于非典型三体性染色体，而在获得性染色体上较为罕见。结论：本研究证实LOH谱分析可通过识别高危亚群优化患者分层，通过揭示不良遗传变异提示预后信息，并有助于预测特定临床特征患者的治疗反应不良。
肿瘤(癌症)患者之家