Abstract 4319: Loss of Golga7 suppresses oncogenic Nras-driven leukemogenesis without detectable toxicity in adult mice

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Abstract NRAS mutations are prevalent in human hematological malignancies and are also common in certain solid tumors, including melanoma and colon cancer. Despite their crucial role in oncogenesis, no effective therapies targeting NRAS have been developed. Inhibiting NRAS localization to the plasma membrane (PM) represents a promising strategy for cancer therapy, as its oncogenic signaling relies on PM localization. Knocking out Golgin subfamily A member 7 (Golga7), an accessory protein of RAS palmitoyltransferases, through a conditional gene editing approach drastically suppresses the development of myeloid leukemia induced by the activation of NrasG12D/G12D knock-in alleles in mice. The loss of Golga7 disrupts NRASG12D PM localization in bone marrow cells without altering the level of NRASG12D palmitoylation. Notably, Golga7 is dispensable for normal hematopoiesis in adult mice. While constitutive Golga7 knockout leads to embryonic lethality, the ubiquitous knockout of Golga7 induced in adult mice does not manifest any measurable toxic effects. These findings indicate that GOLGA7 is an effective and safe therapeutic target for NRAS-driven leukemias. Citation Format: Bo Jiao, Lei Yan, Rui Zhang, Wei Huang, Xinru Wang, Ping Liu, Ruibao Ren. Loss of Golga7 suppresses oncogenic Nras-driven leukemogenesis without detectable toxicity in adult mice [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 4319.

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