Abstract 2088: Prostaglandin E2 signaling promotes adverse survival outcome in B-cell acute lymphoblastic leukemia
Abstract
Obesity increases risk and worsens treatment outcome of acute lymphoblastic leukemia (ALL). To explore how adipose tissue may contribute to these effects, we previously performed single cell RNA sequencing in obese mice to compare gene expression in ALL from adipose tissue to ALL from marrow. We identified 577 differentially expressed genes (DEGs) with a log2-fold threshold of ±0.25 and Bonferroni corrected p-values <0.05. Using ex-vivo coculture of ALL and human adipose explants, we confirmed that adipose tissue upregulates a top DEG, TNFSF11, in ALL cells via secretion of prostaglandin E2 (PGE2). Additionally, we observed that PGE2 conferred modest resistance in vitro to vincristine and daunorubicin chemotherapies. In the present study, we explored whether adipose tissue PGE2 might contribute to poor ALL treatment outcome. We identified six additional genes in the top 50 DEGs that may be induced by PGE2-cAMP signaling and confirmed that these genes were upregulated in vitro by 200 ng/mL PGE2 in BV173 and RS4;11 ALL cell lines (Table)(N=6). To investigate the relevance of these genes to ALL survival, we analyzed data from the TARGET-ALL P2 clinical trial using the NCI GDC Data Portal. TARGET-ALL P2 included pediatric and young adult B-precursor ALL patients treated on Children’s Oncology Group protocols, enriched for patients who experienced relapse within 4 years of diagnosis. Survival and RNAseq expression on diagnostic specimens were available for 466 subjects.…
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