Abstract 3960: Establishment of humanized mouse models engrafted with luciferase-expressing acute myeloid leukemia cell lines

Abstract Introduction: Because acute myeloid leukemia (AML) is a very aggressive and quickly developing cancer, for which actual treatments are either inefficient, poorly tolerated, or leading to resistance, there is a strong need for an effective platform to evaluate novel therapies. Our aim is to provide a relevant humanized mouse model as a precious tool to evaluate innovated treatments to cure AML. Methods: Mice were humanized with CD34+ hematopoietic stem cells to reconstitute a complete human immune system. Three AML cell lines, namely OCI-AML2, OCI-AML3 and MOLM-14, all expressing mCherry and luciferase, were intravenously engrafted at different doses in non-humanized and CD34-humanized mice. Tumor proliferation was monitored by bioluminescence imaging (BLI) thanks to luciferase expression on tumor cells. Their expression of mCherry was also exploited to determine the presence of tumor cells in blood and tissues using flow cytometry. Results: All AML cell lines engrafted in mice, but we observed different growth kinetics and homogeneity depending on the humanization of mice and the dose injected. Indeed, tumor grew more slowly and heterogeneously in humanized mice, which underlines the role of human immune cells reconstituted in mice. This was improved by increasing the number of tumor cells injected. Tumor cells were found in femurs, spleen, kidneys, ovary, lungs, and uterus depending on the cell line. Mice survival was also highly affected by the tumor cell line engrafted. We observed that MOLM14 was the most aggressive model, while OCI-AML3 reached a steady state and were tolerated by mice over a long period. Conclusion: We established 3 different AML cell lines in a model of humanized mice which nicely recapitulates the growth of tumor cells in target organs. These 3 models behave differently in terms of growth kinetic, tolerability by mice, and organs infiltrated, which gives plenty of opportunities to evaluate novel therapies designed to cure AML. Citation Format: Emilie Bayon, Arije Mersni, Audrey Wetzel, Jade Villé, Kiave Yune Ho Wang Yin. Establishment of humanized mouse models engrafted with luciferase-expressing acute myeloid leukemia cell lines abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 3960.