title: Thrombospondin-1 (TSP-1) in primary myelofibrosis (PMF) - a megakaryocyte-derived biomarker which largely discriminates PMF from essential thrombocythemia.
abstract: 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.
authors.affiliation: Institute of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Muth
authors.forename: Bianca M
authors.initials: BM
authors.lastname: Engelhardt
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Kröger
authors.forename: Kais
authors.initials: K
authors.lastname: Hussein
authors.forename: Jérôme
authors.initials: J
authors.lastname: Schlué
authors.forename: Guntram
authors.initials: G
authors.lastname: Büsche
authors.forename: Hans H
authors.initials: HH
authors.lastname: Kreipe
authors.forename: Oliver
authors.initials: O
authors.lastname: Bock
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001706:Biopsy; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D055728:Primary Myelofibrosis / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012042:Registries; D013920:Thrombocythemia, Essential / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019700:Thrombospondin 1 / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019700:Thrombospondin 1