MIAC51 cells induce rapid-onset leukemia across multiple rat strains: A novel and reproducible model of Chloroleukemia

The American Cancer society states leukemia as the most prevalent form of pediatric cancer, nearly 1 in 5 cases of childhood leukemia are acute myeloid leukemia (AML). Advances in risk-group stratification, and chemotherapeutic regimens, have improved clinical outcomes for pediatric patients such that 5-year survival rates are at around 70%. Significant challenges remain in their treatment of leukemia, considering as many as 30% of patients relapse and the expected survival rate is drastically lower. Efforts to understand the mostly unknown etiology of childhood leukemia have been greatly improved by animal modeling which can simulate biological multi-system involvement and a more accurate disease state. We aim to document a new viable animal model in the limited repertoire of AML models using MIAC51 cells, a rat Chloroleukemia cell line. Multiple strains of rat pups, at 7 days old, were injected intraperitoneally with MIAC51 rat cells and compared to respective control groups who received saline solution. All pups had 50 µL of blood drawn at both 7- and 14-days post-injection via tail snip method. Complete blood count (CBC), and differential staining were performed to detect presence of leukemia. At 14 days post-injection, all breeds tested: Wistar, Sprague Dawley, Long Evans, Brown Norway, and Fischer 344, developed leukemia with 100% success rate. Chloroleukemia blasts were found in peripheral blood, indicative of AML as confirmed by Wright stain and CBC. Established here is a novel and reproducible young-rat leukemia model using MIAC51 cells, demonstrating consistent engraftment and leukemic transformation across all tested breeds. Induction of leukemic-state was confirmed by the presence of Chloroleukemia blasts in peripheral blood staining and CBC abnormalities. This model will accelerate translation of hematological science research by providing a platform for studying leukemogenesis, and leukemic pathophysiology in a young-host, with relevance to childhood acute myeloid leukemias. Inquiry into the mechanistic basis for Chloroleukemia induction, and further genetic analysis of the leukemia model will help define its fidelity to human pediatric AML and determine its utility in downstream pre-clinical application.