Role of indoleamine 2,3-dioxygenase in acute myeloid leukemia.

Abstract

Indoleamine 2,3 dioxygenase (IDO), first discovered in the 1960s, is an enzyme that has become a highly investigated metabolic target in cancer research. IDO is the rate-limiting step in tryptophan metabolism catabolism into its byproducts - kynurenines. Both IDO and kynurenines have been implicated in altering the tumor microenvironment, allowing for a tolerogenesis by affecting T-cell maturation and proliferation, and more specifically by inducing differentiation into T regulatory cells. Two mechanisms have been suspected in creating this environment: tryptophan starvation and metabolite toxicity. IDO has been shown to be expressed not only in cancer cells but also in antigen-presenting cells. The exact mechanisms underlying the two different sites of expression have not been fully elucidated. To date, most literature has focused on the role of IDO in solid tumors; we provide a review of IDO and its impact on hematological malignancies - more specifically, acute myeloid leukemia. The pathophysiology of IDO will be discussed, including a summarization of the literature to date on how IDO expression effects prognosis and disease progression in acute myeloid leukemia, along with current IDO-specific therapeutics with future considerations.