Abstract 5967: Overexpression of the transcription factor gene TGIF1 inhibits proliferation in NRAS-driven acute myeloid leukemia cells

Abstract The relatively few oncogenic driver mutations in most acute myeloid leukemia (AML) cells signifies that the numerous phenotypic hallmarks of cancer are established through the dysregulated expression of normal genes, by creating a leukemic transcriptome. We have sought to identify key transcriptional regulators that have the capacity to reprogram the AML transcriptome in ways that promote more normal cell behavior. The AML cell line HL-60 is responsive to treatment with phorbol esters, such as phorbol 12-myristate 13-acetate (PMA), that activate Protein Kinase C (PKC) and result in cell cycle arrest, myeloid differentiation, and eventual apoptosis. Through DNA microarray and RNA sequencing gene expression assays, we have identified approximately 100 genes encoding transcriptional regulators that significantly change in expression level during the PMA response. Among them, the TALE homeobox protein TGIF1 is up-regulated and serves as an expression prognostic marker demonstrating greater overall survival for patients expressing high levels compared to low expression samples by Kaplan-Meier survival plot analyses. Here we show that overexpression through transfection of TGIF1 in AML cell lines inhibits proliferation, as measured by Ki67 and DNA content levels using flow cytometric assays. These findings confirm a tumor suppressor role for TGIF1 in certain AML subtypes as has been previously described in pancreatic cancer. We also provide evidence that the mechanism for TGIF1 proliferation inhibition includes transcriptional repression of MYC and CCND1 expression. A more complete understanding of how TGIF1 directs the AML cell transcriptome is currently in progress using RNA sequencing to identify differentially expressed genes defining TGIF1 targets. Citation Format: Michael Roberts, Herryung Choi, Chase Mitchell Weizer, Helena Holley, Mishra Pranav, Ellsa Hritz, Jeffrey Forrester. Overexpression of the transcription factor gene TGIF1 inhibits proliferation in NRAS-driven acute myeloid leukemia cells [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 5967.