title: Dysregulation of Telomere Lengths and Telomerase Activity in Myelodysplastic Syndrome.
abstract: BACKGROUND
  Telomere shortening is thought to be involved in the pathophysiology of myeloid malignancies, but telomere lengths (TL) during interphase and metaphase in hematopoietic malignancies have not been analyzed. We aimed to assess the TLs of interphase and metaphase cells of MDS and telomerase activity (TA) and to find out prognostic significances of TL and TA.
  
  
  METHODS
  The prognostic significance of TA by quantitative PCR and TL by quantitative fluorescence in situ hybridization (QFISH) of interphase nuclei and metaphase chromosome arms of bone marrow cells from patients with MDS were evaluated.
  
  
  RESULTS
  MDS patients had shorter interphase TL than normal healthy donors (P<0.001). Average interphase and metaphase TL were inversely correlated (P=0.013, p arm; P=0.029, q arm), but there was no statistically significant correlation between TA and TL (P=0.258). The progression free survival was significantly shorter in patients with high TA, but the overall survival was not different according to average TA or interphase TL groups. Multivariable Cox analysis showed that old age, higher International Prognostic Scoring System (IPSS) subtypes, transformation to AML, no history of hematopoietic stem cell transplantation and short average interphase TL (<433 TL) as independent prognostic factors for poorer survival (P=0.003, 0.001, 0.005, 0.005, and 0.013, respectively).
  
  
  CONCLUSIONS
  The lack of correlation between age and TL, TA, and TL, and the inverse relationship between TL and TA in MDS patients reflect the dysregulation of telomere status and proliferation. As a prognostic marker for leukemia progression, TA may be considered, and since interphase TL has the advantage of automated measurement by QFISH, it may be used as a prognostic marker for survival in MDS.
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hee Sue
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Laboratory Medicine, Korea University Anam Hospital, Seoul, Korea.
authors.forename: Jungeun
authors.initials: J
authors.lastname: Choi
authors.affiliation: Cytogenetics Team, Seegene Medical Foundation, Seoul, Korea.
authors.forename: Cha Ja
authors.initials: CJ
authors.lastname: See
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jung Ah
authors.initials: JA
authors.lastname: Kim
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Si Nae
authors.initials: SN
authors.lastname: Park
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Kyongok
authors.initials: K
authors.lastname: Im
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea. soonlee@snu.ac.kr.
authors.forename: Dong Soon
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.|Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea. sangmee1@snu.ac.kr.
authors.forename: Sang Mee
authors.initials: SM
authors.lastname: Hwang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D008297:Male; D008677:Metaphase; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*; D059506:Telomere Shortening
chemical_list: D019098:Telomerase
keywords: Interphase; Metaphase; Myelodysplastic syndrome; Prognosis; Quantitative fluorescence in situ hybridization; Telomerase activity; Telomere length