Myeloma cells contain high levels of inorganic polyphosphate which is associated with nucleolar transcription

• Published in: Haematologica (Roma) 2012-08, Vol.97 (8), p.1264-1271
• Main Authors: Maria D. Jimenez-Nuñez, David Moreno-Sanchez, Laura Hernandez-Ruiz, Alicia Benítez-Rondán, Ana Ramos-Amaya, Beatriz Rodríguez-Bayona, Francisco Medina, José Antonio Brieva, Felix A. Ruiz
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; B-Lymphocytes - metabolism; Biological and medical sciences; Biological Transport; Cell Line, Tumor; Cell Nucleolus - metabolism; Hematologic and hematopoietic diseases; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leupeptins - pharmacology; Medical sciences; Multiple Myeloma - genetics; Multiple Myeloma - metabolism; Original and Brief Reports; Plasma Cells - metabolism; Polyphosphates - metabolism; RNA Polymerase I - metabolism; Transcription, Genetic - drug effects
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2011.051409

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.