The dramatic improvement in the event-free survival of paediatric B-lymphoblastic leukaemia (B-ALL) has led to risk-stratified treatment. Through a combination of clinical features, cytogenetic abnormalities and assessment of treatment response, patients are stratified to receive different intensities of therapy. The presence of high hyperdiploidy (>50 chromosomes) is considered a favourable genetic feature. Conversely, KMT2A fusion genes in B-ALL are associated with a poor prognosis, resulting in intensification of treatment. We present a seven-year-old female with B-ALL, a high hyperdiploid karyotype (56 chromosomes) and KMT2A rearrangement detected on FISH, but with no productive fusion identified. Single nucleotide polymorphism (SNP) array suggested the KMT2A rearrangement was due to chromosome 11 chromothripsis. Subsequent targeted RNA fusion panel and whole transcriptomic sequencing (mRNA-seq) did not detect an expressed KMT2A fusion. Differential expression analyses of the mRNA-seq data led to clustering of this case with other hyperdiploid cases, consistent with the hyperdiploid cytogenetic results. Given the additional intensity and potential toxicity of high-risk treatment, unusual findings by chromosome analysis, FISH and/or chromosomal microarray should prompt consideration of testing for a KMT2A fusion by another method to avoid misclassification.

儿童 B 淋巴细胞白血病 (B-ALL) 无事件生存率的显着改善导致了风险分层治疗的出现。通过结合临床特征、细胞遗传学异常和治疗反应评估，对患者进行分层以接受不同强度的治疗。高超二倍体（> 50 条染色体）的存在被认为是有利的遗传特征。相反， B-ALL 中的KMT2A融合基因与不良预后相关，从而导致治疗强化。我们介绍了一名患有 B-ALL 的 7 岁女性，其具有高超二倍体核型（56 条染色体），并且通过FISH 检测到KMT2A重排，但未发现有效融合。单核苷酸多态性 (SNP) 阵列表明KMT2A重排是由于 11 号染色体染色体碎裂所致。随后的靶向 RNA 融合组和全转录组测序 (mRNA-seq) 未检测到表达的KMT2A融合体。mRNA-seq 数据的差异表达分析导致该病例与其他超二倍体病例聚类，与超二倍体细胞遗传学结果一致。考虑到高风险治疗的额外强度和潜在毒性，染色体分析、FISH 和/或染色体微阵列的异常发现应促使考虑通过其他方法测试 KMT2A 融合，以避免错误分类。