Clinical implication of centrosome amplification and expression of centrosomal functional genes in multiple myeloma

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• 作者：Elena Dementyeva (1)
  Fedor Kryukov (1)
  Lenka Kubiczkova (1)
  Pavel Nemec (1)
  Sabina Sevcikova (1)
  Ivana Ihnatova (2)
  Jiri Jarkovsky (1) (2)
  Jiri Minarik (3)
  Zdena Stefanikova (4)
  Petr Kuglik (1) (5)
  Roman Hajek (1)
  
• 关键词：Multiple myeloma ; Centrosome amplification ; Overall survival
• 刊名：Journal of Translational Medicine
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：11
• 期：1
• 全文大小：573KB
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• 作者单位：Elena Dementyeva (1)
  Fedor Kryukov (1)
  Lenka Kubiczkova (1)
  Pavel Nemec (1)
  Sabina Sevcikova (1)
  Ivana Ihnatova (2)
  Jiri Jarkovsky (1) (2)
  Jiri Minarik (3)
  Zdena Stefanikova (4)
  Petr Kuglik (1) (5)
  Roman Hajek (1)
  
  1. Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5/A3, Brno, 62500, Czech Republic
  2. Institute for Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic
  3. Department of Internal Medicine, University Hospital Olomouc, Olomouc, Czech Republic
  4. Department of Hematology and Blood Transfusion, University Hospital Bratislava, Bratislava, Slovak Republic
  5. Integrated Laboratory of Molecular Cytogenetics, Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic
  

文摘

Background Multiple myeloma (MM) is a low proliferative tumor of postgerminal center plasma cell (PC). Centrosome amplification (CA) is supposed to be one of the mechanisms leading to chromosomal instability. Also, CA is associated with deregulation of cell cycle, mitosis, DNA repair and proliferation. The aim of our study was to evaluate the prognostic significance and possible role of CA in pathogenesis and analysis of mitotic genes as mitotic disruption markers. Design and methods A total of 173 patients were evaluated for this study. CD138+ cells were separated by MACS. Immunofluorescent labeling of centrin was used for evaluation of centrosome amplification in PCs. Interphase FISH with cytoplasmic immunoglobulin light chain staining (cIg FISH) and qRT-PCR were performed on PCs. Results Based on the immunofluorescent staining results, all patients were divided into two groups: CA positive (38.2%) and CA negative (61.8%). Among the newly diagnosed patients, worse overall survival was indicated in the CA negative group (44/74) in comparison to the CA positive group (30/74) (P = 0.019). Gene expression was significantly down-regulated in the CA positive group in comparison to CA negative in the following genes: AURKB, PLK4, TUBG1 (P < 0.05). Gene expression was significantly down-regulated in newly diagnosed in comparison to relapsed patients in the following genes: AURKA, AURKB, CCNB1, CCNB2, CETN2, HMMR, PLK4, PCNT, and TACC3 (P < 0.05). Conclusions Our findings indicate better prognosis for CA positive newly diagnosed patients. Considering revealed clinical and gene expression heterogeneity between CA negative and CA positive patients, there is a possibility to characterize centrosome amplification as a notable event in multiple myeloma pathogenesis.