LAUSR

BACKGROUND: While outcomes for children with acute myeloid leukemia have improved dramatically in recent years, a subset of patients continue to have poor prognosis with METHODS: The TARGET database was utilized to determine expression of mRNAs encoding the TAM family kinases and their ligands, GAS6 and PROS1, in pediatric AML patient samples. Samples (n=145) were categorized into two groups with “high” expression greater than the median or “low” expression less than or equal to the median and overall survival was compared between the two groups using the log-rank test. Expression of TAM family kinases and ligands was determined in AML cell lines by immunoblot. Derivatives of the NB4 AML cell line with shRNA-mediated inhibition of TYRO3 were generated and the impact of TYRO3 inhibition on MERTK levels was determined by immunoblot. RESULTS: High levels of TYRO3 or PROS1 mRNAs in patient samples were independently associated with decreased overall survival in children with AML (p CONCLUSIONS: TYRO3 was ubiquitously expressed in all AML cell lines tested and higher levels of TYRO3 and its ligand PROS1 were associated with significantly poorer prognosis in children with AML. These data suggest a role for TYRO3 in pediatric AML and implicate TYRO3 as a therapeutic target in this context. Citation Format: Sherri K. Smart, Manali Rupji, Bhakti Dwivedi, Jeanne Kowalski, Deborah DeRyckere, Douglas K. Graham. TYRO3 is a potential therapeutic target in pediatric acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2879.