title: Extramedullary relapse of multiple myeloma defined as the highest risk group based on deregulated gene expression data.
abstract: BACKGROUND
  Multiple myeloma (MM) is characterized by malignant proliferation of plasma cells (PC) which accumulate in the bone marrow (BM). The advent of new drugs has changed the course of the disease from incurable to treatable, but most patients eventually relapse. One group of MM patients (10-15%) is considered high-risk because they relapse within 24 months. Recently, extramedullary relapse of MM (EM) has been observed more frequently. Due to its aggressivity and shorter survival, EM is also considered high-risk.
  
  
  OBJECTIVE
  The goal of this study was to determine if the so-called high-risk genes published by the University of Arkansas group (UAMS) are even more deregulated in EM patients than in high-risk MM patients and if these patients may be considered high-risk.
  
  
  METHODS
  Nine samples of bone marrow plasma cells from MM patients as well as 9 tumors and 9 bone marrow plasma cells from EM patients were used. Quantitative real-time PCR was used for evaluation of expression of 15 genes connected to the high-risk signature of MM patients.
  
  
  RESULTS
  Comparison of high-risk plasma cells vs extramedullary plasma cells revealed 4 significantly deregulated genes (CKS1B, CTBS, NADK, YWHAZ); moreover, comparison of extramedullary plasma cells vs extramedullary tumors revealed significant differences in 9 out of 15 genes. Of these, 6 showed significant changes as described by the UAMS group (ASPM, SLC19A1, NADK, TBRG4, TMPO and LARS2).
  
  
  CONCLUSIONS
  Our data suggest that increasing genetic abnormalities as described by the gene expression data are associated with increased risk for EM relapse.
authors: Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.|Department of Clinical Hematology, University Hospital Brno.
authors: Sabina
authors: S
authors: Sevcikova
authors: Institute of Pathological Physiology, 1st Faculty of Medicine, Charles University in Prague.
authors: Helena
authors: H
authors: Paszekova
authors: Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.|Department of Clinical Hematology, University Hospital Brno.
authors: Lenka
authors: L
authors: Besse
authors: Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.|Department of Clinical Hematology, University Hospital Brno.
authors: Lenka
authors: L
authors: Sedlarikova
authors: Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors: Veronika
authors: V
authors: Kubaczkova
authors: Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.|Department of Clinical Hematology, University Hospital Brno.
authors: Martina
authors: M
authors: Almasi
authors: Department of Internal Medicine - Hematooncology, University Hospital Brno.
authors: Ludek
authors: L
authors: Pour
authors: Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.|Department of Clinical Hematology, University Hospital Brno.|Department of Clinical Studies, Faculty of Medicine, University of Ostrava.
authors: Roman
authors: R
authors: Hajek
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002999:Clone Cells; D005260:Female; D015870:Gene Expression; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics*; D010950:Plasma Cells / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D012008:Recurrence
keywords: extramedullary relapse; gene expression; high-risk disease; multiple myeloma; qPCR