Thrombospondin-1 (TSP-1) in primary myelofibrosis (PMF) — a megakaryocyte-derived biomarker which largely discriminates PMF from essential thrombocythemia
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Michaela Muth & Bianca M. Engelhardt & Nicolaus Kröger & Kais Hussein & Jérôme Schlué & Guntram Büsche & Hans H. Kreipe & Oliver Bock
- چاپ و سال / کشور: 2010
Description
Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm showing aberrant bone marrow remodeling with increased angiogenesis, progressive matrix accumulation, and fibrosis development. Thrombospondins (TSP) are factors sharing pro-fibrotic and anti-angiogenic properties, and have not been addressed in PMF before. We investigated the expression of TSP-1 and TSP-2 in PMF related to the stage of myelofibrosis (n=51) and in individual follow-up biopsies by real-time PCR, immunohistochemistry, and confocal laser scanning microscopy (CLSM). TSP-1 was significantly overexpressed (p<0.05) in all stages of PMF when compared to controls. Individual follow-up biopsies showed involvement of TSP-1 during progressive myelofibrosis. TSP-2 was barely detectable but 40% of cases with advanced myelofibrosis showed a strong expression. Megakaryocytes and interstitial proplatelet formations were shown to be the relevant source for TSP-1 in PMF. Stroma cells like endothelial cells and fibroblasts showed no TSP-1 labeling when double-immunofluorescence staining and CLSM were applied. Based on its dual function, TSP-1 in PMF is likely to be a mediator within a pro-fibrotic environment which discriminates from ET cases. On the other hand, TSP-1 is a factor acting (ineffectively) against exaggerated angiogenesis. Both features suggest TSP-1 to be a biomarker for monitoring a PMF-targeted therapy.
Ann Hematol (2011) 90:33–40 DOI 10.1007/s00277-010-1024-z Received: 10 March 2010 / Accepted: 23 June 2010 / Published online: 13 July 2010
