Single Nucleotide Polymorphism Microarray Analysis Unveils Copy‐Number Abnormalities and Genetic Heterogeneity in Malaysian Childhood B‐Cell Precursor Acute Lymphoblastic Leukemia

INTRODUCTION: B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a prevalent pediatric hematologic malignancy characterized by diverse chromosomal aberrations that significantly influence its prognosis. This study aimed to comprehensively characterize the genomic landscape of BCP-ALL in 55 Malaysian patients with BCP-ALL. METHODS: Single-nucleotide polymorphism (SNP) 6.0 microarray and multiplex ligation-dependent probe amplification were utilized to characterize and validate copy-number abnormalities involving key oncogenes, respectively. RESULTS: The SNP 6.0 microarray identified 191 copy-number abnormalities in 55 patients, including common subtypes such as hyperdiploidy (n = 14/191, 7.3%), hypodiploidy (n = 2/191, 1.1%), and various copy-number abnormalities such as interstitial (23.0%), terminal (17.2%), focal (37.1%), and intragenic (18.0%). Notably, intrachromosomal amplification of chromosome 21 (iAMP21) was not observed, suggesting its rarity in this cohort. Comparison with conventional cytogenetic techniques, including Trypsin-Leishman's banding karyotyping, fluorescent in situ hybridization (FISH), and reverse transcription-polymerase chain reaction (RT-PCR), revealed superior resolution of the SNP 6.0 microarray in detecting submicroscopic copy-number abnormalities. Furthermore, MLPA confirmed abnormalities in several oncogenes, including CDKN2A/B, EBF1, ERG, ETV6, IKZF1, JAK2, and PAX5. CONCLUSION: This study demonstrates the utility of combined SNP 6.0 microarray and MLPA in providing a comprehensive and refined understanding of the genetic landscape of BCP-ALL in the Malaysian population. This understanding may facilitate risk stratification and the development of personalized treatment strategies.