title: Marked upregulation of Survivin and Aurora-B kinase is associated with disease progression in the myelodysplastic syndromes.
abstract: BACKGROUND
  Myelodysplastic syndromes are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis. Survivin is a member of the inhibitor of apoptosis family and suppresses apoptosis. Survivin also functions as a subunit of the chromosomal passenger complex for regulating mitosis with Aurora-B. Survivin and Aurora-B play an important role in maintaining genome stability. The aim of this study was to determine the role of Survivin and Aurora-B kinase in disease progression and prognosis of myelodysplastic syndromes.
  
  
  METHODS
  We evaluated the expression levels of these two genes in CD34(+) cells prepared from 64 patients with myelodysplastic syndrome or leukemic blasts from 50 patients with de novo acute myeloid leukemia using quantitative real-time PCR.
  
  
  RESULTS
  Survivin and Aurora-B expression levels were highly correlated with the type of myelodysplastic syndrome, were much higher in refractory anemia with excess blasts-1, refractory anemia with excess blasts-2, and secondary acute myeloid leukemia following myelodysplastic syndrome than in normal control, and increased during disease progression. There was a significant correlation between these expression levels and the International Prognostic Scoring System. Interestingly, these levels were remarkably higher in patients with secondary acute myeloid leukemia following myelodysplastic syndromes than in those with de novo acute myeloid leukemia.
  
  
  CONCLUSIONS
  This is the first report showing that high levels of Survivin and Aurora-B kinase expression in CD34(+) cells are distinctive molecular features of high-risk myelodysplastic syndromes and secondary acute myeloid leukemia following myelodysplastic syndrome. Marked upregulation of Survivin and Aurora-B kinase may contribute to genetic instability and disease progression of myelodysplastic syndromes. Our data may explain why patients with high-risk myelodysplastic syndromes frequently show complex chromosomal abnormality.
authors.affiliation: Department of Hematology and Oncology, Faculty of Medicine, University of Fukui, Japan. ayoshi@u-fukui.ac.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Yoshida
authors.forename: Kouichi
authors.initials: K
authors.lastname: Zokumasu
authors.forename: Yuji
authors.initials: Y
authors.lastname: Wano
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Shin
authors.initials: S
authors.lastname: Imamura
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Takagi
authors.forename: Shinji
authors.initials: S
authors.lastname: Kishi
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Urasaki
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tohyama
authors.forename: Takanori
authors.initials: T
authors.lastname: Ueda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000753:Anemia, Refractory / Q000235:genetics / Q000473:pathology*; D064107:Aurora Kinase B / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000145:classification* / Q000235:genetics / Q000473:pathology*; D016609:Neoplasms, Second Primary / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger; D000077022:Survivin; D064107:Aurora Kinase B