Abstract 90: Development of a systemic Kasumi-3 acute myeloid leukemia model in NSG mice

Abstract

Abstract In vivo models that reproduce human disease are needed for the evaluation of acute myeloid leukemia (AML) disease progression and the development of effective treatments for the disease. The NSG mouse strain is used to model human AML due to the absence of mature B and T lymphocytes and lack of functional NK cells. Successful systemic engraftment of human AML cells in these mice may provide similar disease manifestation observed in patient disease, thus allowing evaluation of therapeutic candidates. The Kasumi-3 cell line from ATCC was established from the blast cells of a myeloperoxidase-negative acute leukemia patient and expresses CD7, CD4, CD13, CD33, CD34, HLA-DR and c-Kit cell surface markers which are compatible with acute myelocytic leukemia, subtype M0 (AML-M0). The prognosis of patients with AML-M0 is poor in comparison to other classifications of AML due to the association of these leukemia cells as being extremely immature and either undifferentiated or minimally differentiated. We have developed a systemic Kasumi-3 human AML model, characterizing tumor cell engraftment over time, following intravenous implantation of Kasumi-3 AML cells in NSG mice. Kasumi-3 cells were implanted at either 1e6 or 10e6 cells per NSG mouse and tumor burden throughout disease progression was assessed by monitoring the engraftment of these cells in the peripheral blood, bone marrow and spleen by FACS analysis. The engraftment of huCD45+ cells was used as a marker for determining the percentage of human tumor cell burden in the mice. Results indicated that within 28 days post intravenous implantation of Kasumi-3 cells at either concentration, huCD45+ cells were present in the peripheral circulation, bone marrow and spleens of NSG mice, and the tumor cell engraftment percentages strongly correlated with the number of implanted Kasumi-3 AML cells. Both the 1e6 and 10e6 cell implant concentrations exhibited unidirectional changes in the percentage of huCD45+ cells engrafting in the peripheral blood, bone marrow, and spleen at all time points throughout the experiment. After analyzing the percentages of human tumor cell engraftment in the NSG mice, the 10e6 Kasumi-3 cell implant concentration showed tumor cell engraftment of 35% in the blood, 67% in the bone marrow and 16% in the spleen on Day 28 and provided the most appropriate environment for the in vivo onset and evaluation of AML tumor burden. The 1e6 Kasumi-3 concentration had a lower percentage of systemic tumor cell engraftment at Day 28 when compared to the percentage of huCD45+ cell engraftment with 10e6 cells. The higher implant concentration showed established tumor burden in the peripheral blood and spleen 14 days sooner than the 1e6 cell dose, which would allow for the observation of efficacy and treatment effects in this model sooner than the 1e6 cell concentration. The establishment of this human AML model in NSG mice can serve as an in vivo tool for the evaluation of putative therapeutics for AML. Citation Format: Diana Chin, Christine Pietsch, Francis McCabe, Susan Chippari, Elizabeth Kaiser, Rebecca Hanson, Mariusz Lubomirski. Development of a systemic Kasumi-3 acute myeloid leukemia model in NSG mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 90. doi:10.1158/1538-7445.AM2014-90