Abstract 5972: Transcriptional dysregulation of pediatric B-ALL derived from Hispanic/Latino patients with and without high-risk genetic structural variants

Abstract Childhood Acute Lymphoblastic Leukemia (ALL) is the most common cancer diagnosis in children and teens. Relapsed ALL still contributes to leading cancer mortality in children and teens with ALL given it is highly prevalent. Hispanic/Latino (H/L) patients are a vulnerable population due to higher incidence of diagnosis and mortality compared to NHW despite correction for socioeconomic risk factors. H/L children have a higher incidence of high-risk genetic structural variants such as BCR-ABL1 translocations. IKZF1-del occurs more frequently and is frequently accompanied by other high-risk translocations or deletions such as CRLF2. CRLF2 translocations along with JAK2 alterations result in high-risk Ph-like B-ALL. We analyzed H/L leukemia samples from 42 H/L children and 18 NHW children using transcriptomics derived from RNAseq to uncover dysregulated regulatory pathways for childhood H/L ALL. We compared these two patient groups based on wildtype IKZF1 status or IKZF1 deleted status. Using ranked gene set enrichment analysis we found increased representation of dysregulated pathways for multiple genome maintenance pathways that affect replication, repair, and histone modification in H/L B-ALL with IKZF1 deletion. When comparing samples from H/L and NHW with wildtype IKZF1, gene set enrichment analysis showed downregulated showed increased dysregulated expression of DNA repair, cell cycle regulation, as well as amino acid metabolism pathways. Reduced representation bisulfide sequencing analysis of equal H/L and NWH B ALL samples (n = 16) showed altered methylation signatures for H/L patients in comparison to NHW for genes represented in cytoskeletal structure, vesicle trafficking, cancer cell signaling, amino acid response pathways, and long noncoding RNAs associated with cancer. The data show that there are some fundamental differences in the transcriptomics and transcriptomic regulation of B-ALL derived H/L patients compared to that of NWH. This was observed even in the absence of high-risk genetic structural variants. The H/L B-ALL results suggest that further research into the mechanisms of this transcriptional dysregulation will result in new approaches for risk adapted therapy to address this vulnerable population. Citation Format: Joseph Schramm, Brindangnanam Pownraj, Bing He, Yali Ding, Daniel Bogush, Singh Chingakham, Katarina Dovat, Diwakar Bastihalli Tukaramrao, Sinisa Dovat. Transcriptional dysregulation of pediatric B-ALL derived from Hispanic/Latino patients with and without high-risk genetic structural variants [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 5972.