Reilly J T, Barnett D, Dolan G, Forrest P, Eastham J, Smith A
Department of Haematology, Northern General Hospital, Sheffield.
Br J Haematol. 1993 Jan;83(1):58-62. doi: 10.1111/j.1365-2141.1993.tb04631.x.
The current hypothesis for the pathogenesis of myelofibrosis involves the intramedullary release of growth factors from defective or abnormal megakaryocytes. We describe a case of an acute micromegakaryocytic leukaemia, in a patient with chronic myelofibrosis, that provides additional evidence for this concept. The micromegakaryocytes, which reached 223 x 10(9)/l, were characterized morphologically by both light and electron microscopy, immunocytochemically and by platelet peroxidase activity. The cells were shown to have a mature cytoplasm, containing alpha granules and the associated proteins; vWF:Ag, fibrinogen, fibronectin and protein S. DNA analysis, by both a Seescan Solitaire Plus image analysis system and flow cytometry, revealed nuclear immaturity, with 92% of cells being diploid. Serum markers of connective tissue synthesis, namely carboxy terminal peptide of procollagen I (PICP), procollagen terminal peptide III (PIIIP) and laminin all increased significantly following transformation and were associated with an increase in platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta). These observations support the current hypothesis for bone marrow fibrosis formation and provide, for the first time, a link between in vivo growth factor release, bone marrow stromal turnover and megakaryocyte mass. In addition, the release of biologically active TGF-beta may explain both the increased fibronectin and angiogenesis characteristic of myelofibrotic bone marrow.
目前关于骨髓纤维化发病机制的假说认为，生长因子由有缺陷或异常的巨核细胞在骨髓内释放。我们描述了1例患有慢性骨髓纤维化的急性微巨核细胞白血病患者，该病例为这一概念提供了更多证据。微巨核细胞计数达223×10⁹/L，通过光学显微镜和电子显微镜、免疫细胞化学及血小板过氧化物酶活性对其进行形态学特征分析。结果显示，这些细胞具有成熟的细胞质，含有α颗粒及相关蛋白，如血管性血友病因子抗原（vWF:Ag）、纤维蛋白原、纤连蛋白和蛋白S。通过Seescan Solitaire Plus图像分析系统和流式细胞术进行DNA分析，结果显示细胞核不成熟，92%的细胞为二倍体。转化后，结缔组织合成的血清标志物，即I型前胶原羧基末端肽（PICP）、III型前胶原末端肽（PIIIP）和层粘连蛋白均显著升高，并与血小板衍生生长因子（PDGF）和转化生长因子-β（TGF-β）的增加相关。这些观察结果支持了目前关于骨髓纤维化形成的假说，并首次在体内生长因子释放、骨髓基质更新和巨核细胞数量之间建立了联系。此外，生物活性TGF-β的释放可能解释了骨髓纤维化骨髓中纤连蛋白增加和血管生成的特征。
