Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer and ranks fifth in incidence in Northern Brazil. Owing to its high genomic heterogeneity, molecular cytogenetics—particularly chromosomal copy number variation (CNV) analysis—has advanced understanding of disease progression. Genes such as IKZF1, PAX5, and CDKN2A are recurrently altered in B-ALL and influence malignancy through roles in differentiation and cell cycle regulation. Microarray profiling of ALL samples from a regional oncology center revealed consistent CNV events in the ADAM (A Disintegrin And Metalloproteinase) gene family, known to mediate tumor progression, invasion, and therapeutic resistance in several cancers. Its role in ALL, however, remains largely uncharacterized. These findings highlight ADAM genes as potential biomarkers and therapeutic targets, warranting further functional and clinical investigation to elucidate their contribution to ALL pathogenesis.

To investigate patterns of chromosomal alterations in pediatric ALL patients, with a focus on the ADAM gene family, and to describe potential related impacts.

Sixteen samples from pediatric patients diagnosed with ALL were analyzed. Genomic DNA was extracted using the Pure Link Genomic DNA Mini Kit (Invitrogen, California, USA). The aCGH analysis was performed using the Agilent 4x180k CGH + SNP microarray (Santa Clara, USA). Following extraction, the DNA was digested with a restriction enzyme and labeled with the Cy5 fluorochrome, employing random primers and the exo-Klenow fragment DNA polymerase. Control DNA was labeled with the Cy3 fluorochrome. Patient and control DNA samples were combined and hybridized onto the microarray. Data interpretation was carried out using Agilent’s CytoGenomics v5.0 software.

Alterations were identified in at least one member of the ADAM family and on different chromosomes in all patients analyzed by aCGH. Notably, ADAM6 showed 23 occurrences (gain and amplification effects), ADAM3A showed 10 occurrences (deletion, loss, and amplification effects), and ADAM5P showed 9 occurrences (deletion, loss, and amplification effects), with emphasis on chromosomal regions 14q32.33 and 8p11.22.

Amplification of ADAM6 may enhance growth factor– and cell surface receptor–dependent processes that reinforce pro-proliferative signaling pathways and anti-apoptotic mechanisms in lymphoid blasts, suggesting a stronger association with B-lineage ALL. Conversely, losses of ADAM3A and ADAM5P may impair cell adhesion and remodeling of the bone marrow microenvironment, facilitating immune evasion, expansion of aberrant clones, and migration of these cells into the peripheral blood. Although numerous reports have linked mutations in these genes to renal, lung, and breast cancers, their roles in leukemia remain poorly characterized. The findings presented here demonstrate a strong association between the ADAM gene family and ALL patients, suggesting that ADAM dysfunction contributes to the pathogenesis of this malignancy and identifies these genes as potential targets for functional studies and therapeutic interventions. While larger studies are warranted, the data obtained from this pediatric cohort underscore the need to further explore the mutational profile of this population.