Ismail Azli, Ahid Fadly, Moi Wong Nyuk, Kamaluddin Nor Rizan, Esa Ezalia, Yusoff Yuslina Mat, Seman Zahidah Abu, Mohammed Muhammad Asyraff, George Elizabeth, Isa Asmida, Zakaria Zubaidah
Hematology Unit, Cancer Research Centre, Institute for Medical Research, National Institutes of Health, Ministry of Health Malaysia, Shah Alam, Selangor, 40170, Malaysia.
Centre for Medical Laboratory Technology Studies, Faculty of Health Sciences, Universiti Teknologi MARA, Puncak Alam, Selangor, 42300, Malaysia.
Mol Cytogenet. 2025 Mar 28;18(1):7. doi: 10.1186/s13039-025-00709-4.
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, comprising approximately 25% of pediatric malignancies. Notably, chromosomal aberrations and genetic alterations play a central role in the pathogenesis of ALL, serving as critical diagnostic and prognostic markers. In this study, we use array-based comparative genomic hybridization (array-CGH) to explore the landscape of copy number variations (CNVs) and variants of uncertain significance (VUS) in 67 Malaysian childhood ALL patients with normal karyotype.
A total of 36 pathogenic CNVs (26 gains, 10 losses) were identified in 19 (28.4%) patients which harbor genes related to the development of ALL. The genes include the MLLT3 (9p21.3), ETV6 (12p13.2), RUNX1 (21q22.12), ERG (21q22.2) and DMD (Xp21.1). On the other hand, a total of 46 variants of uncertain significance (VUS) was observed in 34 (50.7%) patients.
Our study indicates that array-CGH is able to identify and characterize the CNVs responsible for the pathogenesis of childhood ALL. However, further studies are required to determine the pathogenic implications of VUS in the development of childhood ALL.
急性淋巴细胞白血病（ALL）是儿童期最常见的癌症，约占小儿恶性肿瘤的25%。值得注意的是，染色体畸变和基因改变在ALL的发病机制中起核心作用，是关键的诊断和预后标志物。在本研究中，我们使用基于芯片的比较基因组杂交技术（array-CGH）来探究67例核型正常的马来西亚儿童ALL患者的拷贝数变异（CNV）和意义未明变异（VUS）情况。
在19例（28.4%）患者中总共鉴定出36个致病CNV（26个增益，10个缺失），这些患者携带与ALL发生相关的基因。这些基因包括MLLT3（9p21.3）、ETV6（12p13.2）、RUNX1（21q22.12）、ERG（21q22.2）和DMD（Xp21.1）。另一方面，在34例（50.7%）患者中总共观察到46个意义未明变异（VUS）。
我们的研究表明，array-CGH能够识别和表征导致儿童ALL发病机制的CNV。然而，需要进一步研究来确定VUS在儿童ALL发生中的致病意义。
