title: Increased expression of interferon signaling genes in the bone marrow microenvironment of myelodysplastic syndromes.
abstract: BACKGROUND
  The bone marrow (BM) microenvironment plays an important role in the pathogenesis of myelodysplastic syndromes (MDS) through a reciprocal interaction with resident BM hematopoietic cells. We investigated the differences between BM mesenchymal stromal cells (MSCs) in MDS and normal individuals and identified genes involved in such differences.
  
  
  METHODS
  BM-derived MSCs from 7 MDS patients (3 RCMD, 3 RAEB-1, and 1 RAEB-2) and 7 controls were cultured. Global gene expression was analyzed using a microarray.
  
  
  RESULTS
  We found 314 differentially expressed genes (DEGs) in RCMD vs. control, 68 in RAEB vs. control, and 51 in RAEB vs. RCMD. All comparisons were clearly separated from one another by hierarchical clustering. The overall similarity between differential expression signatures from the RCMD vs. control comparison and the RAEB vs. control comparison was highly significant (p = 0), which indicates a common transcriptomic response in these two MDS subtypes. RCMD and RAEB simultaneously showed an up-regulation of interferon alpha/beta signaling and the ISG15 antiviral mechanism, and a significant fraction of the RAEB vs. control DEGs were also putative targets of transcription factors IRF and ICSBP. Pathways that involved RNA polymerases I and III and mitochondrial transcription were down-regulated in RAEB compared to RCMD.
  
  
  CONCLUSIONS
  Gene expression in the MDS BM microenvironment was different from that in normal BM and exhibited altered expression according to disease progression. The present study provides genetic evidence that inflammation and immune dysregulation responses that involve the interferon signaling pathway in the BM microenvironment are associated with MDS pathogenesis, which suggests BM MSCs as a possible therapeutic target in MDS.
authors: Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea; Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Miyoung
authors: M
authors: Kim
authors: Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors: Seungwoo
authors: S
authors: Hwang
authors: Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors: Kiejung
authors: K
authors: Park
authors: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Seon Young
authors: SY
authors: Kim
authors: Department of Laboratory Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea; Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Republic of Korea.
authors: Young Kyung
authors: YK
authors: Lee
authors: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Dong Soon
authors: DS
authors: Lee
mesh_terms: D000328:Adult; D000368:Aged; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology*; D060833:Cellular Microenvironment / Q000235:genetics*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007372:Interferons / Q000378:metabolism*; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome
chemical_list: D014157:Transcription Factors; D007372:Interferons