Unidad de Investigación, 9 Planta, Hospital Universitario Puerta del Mar, Avenida Ana de Viya 21, 11009 Cádiz, Spain.
Haematologica. 2012 Aug;97(8):1264-71. doi: 10.3324/haematol.2011.051409. Epub 2012 Feb 7.
In hematology there has recently been increasing interest in inorganic polyphosphate. This polymer accumulates in platelet granules and its functions include modulating various stages of blood coagulation, inducing angiogenesis, and provoking apoptosis of plasma cells. In this study we evaluated the characteristics of intracellular polyphosphate in myeloma cell lines, in primary myeloma cells from patients, and in other human B-cell populations from healthy donors.
We have developed a novel flow cytometric method for detecting levels of polyphosphate in cell populations. We also used confocal microscopy and enzymatic analysis to study polyphosphate localization and characteristics.
We found that myeloma plasma cells contain higher levels of intracellular polyphosphate than normal plasma cells and other B-cell populations. Localization experiments indicated that high levels of polyphosphate accumulate in the nucleolus of myeloma cells. As the principal function of the nucleolus involves transcription of ribosomal DNA genes, we found changes in the cellular distribution of polyphosphate after the inhibition of nucleolar transcription. In addition, we found that RNA polymerase I activity, responsible for transcription in the nucleolus, is also modulated by polyphosphate, in a dose-dependent manner.
Our results show an unusually high accumulation of polyphosphate in the nucleoli of myeloma cells and a functional relationship of this polymer with nucleolar transcription.
在血液学领域，人们对无机多聚磷酸盐的兴趣近来与日俱增。这种聚合物在血小板颗粒中积累，其功能包括调节血液凝固的各个阶段、诱导血管生成和诱导浆细胞凋亡。在这项研究中，我们评估了骨髓瘤细胞系、患者原代骨髓瘤细胞以及来自健康供体的其他人类 B 细胞群体中的细胞内多聚磷酸盐的特征。
我们开发了一种用于检测细胞群体中多聚磷酸盐水平的新型流式细胞术方法。我们还使用共聚焦显微镜和酶分析来研究多聚磷酸盐的定位和特征。
我们发现骨髓瘤浆细胞比正常浆细胞和其他 B 细胞群体含有更高水平的细胞内多聚磷酸盐。定位实验表明，多聚磷酸盐高水平积聚在骨髓瘤细胞的核仁中。由于核仁的主要功能是转录核糖体 DNA 基因，我们发现核仁转录抑制后多聚磷酸盐在细胞内的分布发生变化。此外，我们发现负责核仁转录的 RNA 聚合酶 I 活性也被多聚磷酸盐以剂量依赖的方式调节。
我们的结果显示骨髓瘤细胞的核仁中异常高积聚多聚磷酸盐，并且这种聚合物与核仁转录之间存在功能关系。
