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The effect of high dietary eicosapentaenoic acid supplementation in leukemic mice

Current chemotherapies for treatment of chronic myelogenous leukemia (CML) do not eliminate leukemic stem cells (LSCs), leading to relapse of the disease. Discovery of alternative therapies to target LSCs is essential for elimination of the disease. We have recently reported on the endogenous production of increased levels of a novel anti‐inflammatory cyclopentenone prostaglandin Δ12‐ prostaglandin J3 (Δ12‐PGJ3), by macrophages cultured with eicosapentaenoic acid (EPA). The levels of EPA used in our studies reflect the doses prescribed by the FDA. To effectively translate these studies, we report here the endogenous production of Δ12‐PGJ3 in mice on high EPA using LC‐MS/MS. Furthermore, we report the effect of high EPA on progression of leukemia and the ability of endogenous metabolites to target the LSCs in a CML model where the hematopoietic stem cells expressing the fusion oncoprotein Bcr‐Abl are transplanted into such mice. Pathways of apoptosis activated by Δ12‐PGJ3 will be discussed.