Abstract 505: Differences in gene expression across races in pediatric T-cell acute lymphoblastic leukemia (T-ALL)
Authors: Rishabh Gaur, Irina Pushel, Midhat Farooqi
Journal: Cancer Research (2025)

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is a malignancy of immature T-cells characterized by rapid proliferation of leukemic cells in the bone marrow and blood. Despite significant advancements in the understanding and treatment of B-cell acute lymphoblastic leukemia (B-ALL), T-ALL remains comparatively underexplored, with limited data on the underlying genomic alterations driving disease progression. T-ALL constitutes 12-15% of pediatric and adult ALL cases, with poorer outcomes than B-ALL. Understanding differential gene expression in T-ALL is critical, especially with respect to how these may differ across racial groups, as African Americans and Asians have been shown to have lower survival than Caucasians. In this study, we analyzed RNA sequencing data from a cohort of pediatric T-ALL patients to identify differences in gene expression patterns between racial groups, specifically focusing on Caucasian, Asian, and African American patients. Using DESeq2, differential gene expression analysis was performed across racial categories. A total of 37 patients with genomic data were included, with expression counts normalized, and statistical significance was determined based on adjusted p-values &amp;lt;0.05. We also examined potential correlations between gene expression and clinical outcomes such as relapse status. Preliminary results identified several genes exhibiting significant differential expression between racial groups. 250 genes, mostly related to the adaptive immune system, were significantly differentially expressed in Caucasian vs African American patients. 261 genes, mostly related to homeostasis and cellular development, showed differential expression in Caucasian vs Asian patients. There was an overlap of 17 genes which were differentially expressed in all three races. Importantly, FAT1 was one of these 17 genes, as it is a gene that has previously been implicated in T-ALL but not studied with regard to differences in expression by race. Preliminary analyses also found differentially expressed genes between African American vs Asian and relapse vs non-relapse. Additional studies are ongoing to determine the specificity of all these genes to T-ALL and to compare the genes that were differentially expressed across various races to the genes differentially expressed across outcomes. This study highlights the importance of examining racial differences in gene expression within T-ALL, a leukemia subtype that has not been extensively understood. The identification of race-specific gene expression profiles may provide insights into the biological mechanisms that contribute to differences in clinical outcomes and response to treatment. Future work will focus on validating these findings in larger, independent cohorts and exploring how these genetic differences may influence disease progression, ultimately reducing racial disparities in T-ALL survival. Citation Format: Rishabh Gaur, Irina Pushel, Midhat Farooqi. Differences in gene expression across races in pediatric T-cell acute lymphoblastic leukemia (T-ALL) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 505.