Uncovering LINC02982: a T-ALL-specific lncrna linking epigenetic regulation and metabolic pathways

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive pediatric malignancy with limited molecular biomarkers to guide diagnosis and personalized therapy. Given the critical role of long non-coding RNAs in gene regulation and chromatin dynamics, we investigated whether novel lncRNAs could contribute to T-ALL pathogenesis. Through transcriptomic profiling of patient samples and in-silico validation on public datasets, we identified LINC02982 as a lncRNA selectively overexpressed in T-ALL and specifically enriched in leukemic blasts. Functional silencing of LINC02982 in multiple T-ALL cell lines impaired proliferation, altered cell-cycle progression, and increased apoptosis. Integrative ATAC-seq and RNA-seq analyses revealed widespread changes in chromatin accessibility and gene expression, including deregulation of metabolic genes such as AK4 and PSAT1. Promoter accessibility showed a moderate correlation with transcriptional changes, consistent with a potential cis-regulatory role, while broader transcriptomic alterations suggest additional trans effects. Pathway analysis highlighted metabolic processes, including cholesterol biosynthesis, as significantly affected, with LINC02982 depletion reducing expression of key pathway genes and intracellular cholesterol levels. These findings identify LINC02982 as a T-ALL-associated lncRNA linked to transcriptional and metabolic alterations, supporting its potential biological relevance in leukemic cellular regulation and warranting further investigation in larger clinical cohorts.