CML cell trafficking: Influence of the stromal microenvironment

Chronic myeloid leukemia (CML) is a malignancy of hematopoietic stem cells. The disease is characterized by abnormal (excessive) proliferation and aberrant trafficking of transformed progenitor cells. This includes early release of these cells into the bloodstream of patients, which is likely due- at least in part- to adhesion receptor abnormalities that affect the interaction of malignant cells with bone marrow stroma and important extracellular matrix proteins. Aberrant trafficking is also contrarily characterized by homing of transformed cells to stroma in the bone marrow and spleen and other tissue sources characterized by high stromal content. This is a fate that- due to the cytoprotective effect of stroma on drug-treated leukemia cells- can lead to development of minimal residual disease in patients undergoing therapy with targeted inhibitors such as imatinib and nilotinib. This review will briefly discuss these events, as well as novel therapeutic strategies designed to override stroma-associated drug resistance in CML.