Priest_2025_Toxicol.Pathol__1926233251350661

This report presents the findings of a spontaneous case of acute myeloid leukemia (AML) in a 6-year-old male cynomolgus macaque enrolled in a 9-month repeat dose-toxicity and toxicokinetic study. Abnormal hematology findings occurred approximately 6 months into daily oral dosing that included markedly decreased red blood cell mass and reticulocyte count, moderately decreased platelet counts, and the identification of abnormal cells in blood that were interpreted as neoplastic. Cytologic characteristics of the neoplastic cells included a moderate to high nucleus to cytoplasm ratio, medium to deep blue cytoplasm, and a round to oval nucleus with fine chromatin, often with multiple, irregularly shaped nucleoli. Following humane euthanasia, evaluation of bone marrow smears and formalin fixed paraffin embedded tissues revealed neoplastic cells of similar morphology. A panel of immunohistochemistry and cytochemical stains demonstrated expression of CD68 and myeloperoxidase, with weaker and less consistent expression of CD11c and CD45. No staining was detected for CD34, CD14, and T (CD3) and B (CD20) lymphoid markers. The neoplastic cells did not stain for any of the cytochemical stains applied (Periodic Acid Schiff, alpha-naphthyl acetate esterase, Sudan Black B, alpha-naphthyl butyrate esterase, and chloroacetate esterase). An interpretation of AML was made suggestive of a myelomonocytic lineage.