Arginase-mediated "field" defects in AML.

In this issue of Blood, Mussai et al report on the ability of acute myeloid leukemia (AML) blasts to inhibit the immune system and hematopoiesis through aberrantly high levels of arginase II activity.1 AML is a clinically, genetically, and epigenetically heterogeneous disease.2 Both epigenetic and genetic aberrations in AML blasts have been used to understand mechanisms of leukemia growth and predict patients' outcomes, as well as assign them to different treatment approaches. However, the majority of patients treated with chemotherapy and/or molecular targeting agents continue to die of their disease. Stem cell transplantation (SCT) has been proven effective in curing AML by allowing for the administration of otherwise myeloablative and toxic doses of chemotherapy and for reconstitution of an effective immune system from the donor graft that, in turn, contributes to the eradication of resistant clonal cell subpopulations. These populations may include those with high self-renewal ability: the so-called leukemia stem (or initiating) cells. However, even following SCT, patients may relapse and die of their disease, underlying the complexity of AML biology and of the mechanisms of disease resistance.