Acute myelogenous leukemia-microenvironment interactions: Role of endothelial cells and proteasome inhibition

How leukemia progenitors interact with marrow microenvironment components is poorly understood. In this work, the effects of endothelial coculture on acute myelogenous leukemia (AML) blast survival is examined as are the effects of endothelial coculture on the impact of a cytotoxic agent such as cytarabine. Similar to marrow stromal cells, endothelial cells are able to increase survival and proliferation of AML blasts and to partially protect against cytarabine effects. The proteasome inhibitor, bortezomib, has inhibitory effects in multiple myeloma in part through effects on marrow stromal cells. Bortezomib has been found to inhibit AML blast survival. Such inhibition is less, however, in the presence of endothelial monolayers. Furthermore, AML blast transmigration through human umbilical vein endothelial cells is inhibited by bortezomib. These studies demonstrate that AML is subject to influence of endothelial cells and of agents such as bortezomib which have potential impact on AML interaction with the microenvironmental niche.