Disease progression mechanism in myelodysplastic syndromes: Insight into the role of the microenvironment

The somatic mutation theory proposing that a sequential accumulation of genetic abnormalities plays a major role in cancer pathogenesis has not yet been confirmed for myelodysplastic syndromes (MDS). Meanwhile, recent data in some cancers has underscored the role of the microenvironment in tumor growth. MDS CD34+CD38- cells usually fail to repopulate after transplantation in mice, suggesting the importance of the microenvironment for MDS cells. Our recent data have provided a disease-progression model in which overproduction of interferon-gamma and tumor necrosis factor-alpha in the microenvironment is the primary event. This causes B7-H1 molecule expression on MDS blasts, which generates a bifunctional signal inducing T-cell apoptosis and enhancing blast proliferation. The latter may provide more opportunity for developing secondary genetic changes. (C) 2011 Elsevier Ltd. All rights reserved.