title: Disease progression mechanism in myelodysplastic syndromes: insight into the role of the microenvironment.
abstract: 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-γ and tumor necrosis factor-α 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.
authors.affiliation: Division of Hematology, Department of Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Ishibashi
authors.forename: Hideto
authors.initials: H
authors.lastname: Tamura
authors.forename: Kiyoyuki
authors.initials: K
authors.lastname: Ogata
mesh_terms: D000818:Animals; D017209:Apoptosis; D060890:B7-H1 Antigen / Q000378:metabolism*; D001752:Blast Crisis; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D009190:Myelodysplastic Syndromes / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D059016:Tumor Microenvironment; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D060890:B7-H1 Antigen; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma