Ann Lab Med.  2017 May;37(3):195-203. 10.3343/alm.2017.37.3.195.

Dysregulation of Telomere Lengths and Telomerase Activity in Myelodysplastic Syndrome

  • 1Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.
  • 2Department of Laboratory Medicine, Korea University Anam Hospital, Seoul, Korea.
  • 3Cytogenetics Team, Seegene Medical Foundation, Seoul, Korea.
  • 4Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
  • 5Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.


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.
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.
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).
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.


Interphase; Metaphase; Telomere length; Telomerase activity; Myelodysplastic syndrome; Quantitative fluorescence in situ hybridization; Prognosis

MeSH Terms

Bone Marrow Cells
Disease-Free Survival
Hematologic Neoplasms
Hematopoietic Stem Cell Transplantation
In Situ Hybridization
Myelodysplastic Syndromes*
Polymerase Chain Reaction
Telomere Shortening
Tissue Donors


  • Fig. 1 Quantitative fluorescence in situ hybridization (QFISH) to detect telomere length in interphase (A), metaphase (B). QFISH was performed by using Cy3-PNA probe (red) on telomere and the fluorescein isothiocyanate (FITC)-labeled peptide nucleic acid (PNA) probe (green) on centromere of chromosome 2 in interphase (A) and metaphase (B) of patient with trisomy 8.

  • Fig. 2 The correlation of interphase telomere length (TL), metaphase TL, and age. (A) The linear regression model for age and interphase TL. (B) The linear regression model for age and metaphase p arm and q arm TLs. (C) The correlation between interphase TL and metaphase TL. The correlation coefficient for interphase TL and metaphase p arm TL is −0.498, P=0.013 and for interphase TL and metaphase q arm TL, −0.445, P=0.029. TL plotted is the telomere/centromere fluorescence intensity ratio.

  • Fig. 3 Progression-free survival and overall survival according to telomerase activity (TA) and the interphase telomere lengths (TL). Time to progression to AML for patients with high (≥average) and low (


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