Ann Lab Med 2017; 37(3): 195-203  https://doi.org/10.3343/alm.2017.37.3.195
Dysregulation of Telomere Lengths and Telomerase Activity in Myelodysplastic Syndrome
Hee Sue Park, M.D.1, Jungeun Choi, M.T.2, Cha-Ja See, M.T.3, Jung-Ah Kim, M.D.1, Si Nae Park, M.S,4, Kyongok Im, M.T.4, Sung-Min Kim, B.S.4, Dong Soon Lee, M.D.1,4, and Sang Mee Hwang, M.D.1,5
Department of Laboratory Medicine1, Seoul National University College of Medicine, Seoul; Department of Laboratory Medicine2, Korea University Anam Hospital, Seoul; Cytogenetics Team3, Seegene Medical Foundation, Seoul; Cancer Research Institute4, Seoul National University College of Medicine, Seoul; Department of Laboratory Medicine5, Seoul National University Bundang Hospital, Seongnam, Korea
Correspondence to: Sang Mee Hwang
Department of Laboratory Medicine, Seoul National University Bundang Hospital, 82 Gumiro 173 beongil, Bundang-gu, Seongnam 13620, Korea
Tel: +82-31-787-7694
Fax: +82-31-787-4015
E-mail: sangmee1@snu.ac.kr
Dong Soon Lee
Department of Laboratory Medicine, Seoul National University College of Medicine, 101 Daehak-ro Jongno-gu, Seoul 03080, Korea
Tel: +82-2-2072-3986
Fax: +82-2-747-0359
E-mail: soonlee@snu.ac.kr
Received: August 11, 2016; Revised: October 4, 2016; Accepted: January 12, 2017; Published online: May 1, 2017.
© The Korean Society for Laboratory Medicine. All rights reserved.

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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.
Keywords: Interphase, Metaphase, Telomere length, Telomerase activity, Myelodysplastic syndrome, Quantitative fluorescence in situ hybridization, Prognosis


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