Role of Microenvironment in Resistance to Therapy in AML.

As part of the dynamic interactions between leukemic cells and cells of the bone marrow microenvironment, specific niches provide a sanctuary where subpopulations of leukemic cells evade chemotherapy-induced death and acquire a drug-resistant phenotype. This review focuses on the cellular and molecular biology of the leukemia stem cell (LSC) niche and of microenvironment/leukemia interactions. Key emerging therapeutic targets include chemokine receptors, adhesion molecules, the sympathetic nervous system, and hypoxia-related proteins, as well as the genetic and epigenetic abnormalities of the leukemia-associated stroma. The complex interplay between LSCs and microenvironment components provides a rationale for appropriately tailored molecular therapies designed to improve outcomes in leukemia. Further understanding of the contribution of the bone marrow niche to the process of leukemogenesis may provide new targets that allow destruction of LSCs without adversely affecting normal stem cell self-renewal.