Institute of Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
Ann Hematol. 2011 Jan;90(1):33-40. doi: 10.1007/s00277-010-1024-z. Epub 2010 Jul 13.
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.
原发性骨髓纤维化（PMF）是一种慢性骨髓增生性肿瘤，表现为异常的骨髓重构，伴有血管生成增加、基质积累进行性进展和纤维化发展。血小板反应蛋白（TSP）是具有促纤维化和抗血管生成特性的因子，在 PMF 中尚未得到研究。我们通过实时 PCR、免疫组织化学和共聚焦激光扫描显微镜（CLSM）研究了 TSP-1 和 TSP-2 在与骨髓纤维化阶段相关的 PMF（n = 51）和个体随访活检中的表达。与对照组相比，TSP-1 在 PMF 的所有阶段均显著过表达（p < 0.05）。个体随访活检显示 TSP-1 在进行性骨髓纤维化过程中存在。TSP-2 几乎检测不到，但 40%的晚期骨髓纤维化病例表现出强烈的表达。研究表明，巨核细胞和成纤维细胞等间质细胞在 PMF 中是 TSP-1 的相关来源。当应用双免疫荧光染色和 CLSM 时，内皮细胞和成纤维细胞等基质细胞没有 TSP-1 标记。基于其双重功能，PMF 中的 TSP-1 可能是促纤维化环境中的一种介质，与 ET 病例不同。另一方面，TSP-1 是一种针对过度血管生成的（无效）作用因子。这两个特征都表明 TSP-1 可作为监测 PMF 靶向治疗的生物标志物。
