Abstract 1068: Navigating next-generation pre-clinical models of drug discovery & development with RNA-seq

Cell models paired with curated gene expression data are vital for preclinical research. Transcriptomic data from traceable, authenticated cell lines streamline hypothesis development and experimental design while illuminating underlying biological mechanisms. In cancer research, these models have notably identified therapeutic targets and biomarkers. To advance cancer research, ATCC® sequenced the transcriptomes of 141 immune cancer cell lines, accessible through ATCC Cell Line Land, encompassing various hematopoietic lineages. This effort provided insights into gene expression patterns, revealing potential biomarkers and gene regulatory networks tailored to specific cell lines. Utilizing this data, we conducted a comparative analysis, pinpointing genes and pathways governing cellular traits. This informed our evaluation of therapeutic molecules like the Curcumin analog EF-24. Our analysis of EF-24's effects on leukemia cell lines K562 (ATCC® CCL-243™, HL-60 (ATCC® CCL-240™), THP-1 (ATCC® TIB-202™), Kasumi-1 (ATCC® CRL-2724™) demonstrated increased cell death post-treatment. EF-24 activated pathways associated with cell survival and death regulation, notably impacting STAT1-induced cell death, and enhancing innate immune system genes. This research offers a detailed understanding of EF-24's molecular actions in tumors, emphasizing the significance of STAT1 signaling in its antitumorigenic effects. The profound impact of EF-24 on inducing cell death across multiple leukemia cell lines underscores its potential as a therapeutic agent. By elucidating its specific molecular actions and highlighting the pivotal role of STAT1 signaling, this study not only deepens our comprehension of EF-24's mechanisms but also underscores its promising value in targeted antitumorigenic strategies. Citation Format: Ajeet P. Singh, Rula R. Khairi, Amy L. Reese, Jade Kirkland, James Duncan, Noah Wax, Robert Marlow, Steve King, Ana Fernandes, Jonathan L. Jacobs. Navigating next-generation pre-clinical models of drug discovery & development with RNA-seq [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 1068.