Telomere stability is frequently impaired in high-risk groups of patients with myelodysplastic syndromes

Junko H. Ohyashiki, Hiroshi Iwama, Naoyuki Yahata, Keiko Ando, Shigefumi Hayashi, Jerry W. Shay, Kazuma Ohyashiki

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Genomic instability induces an accumulation of genetic changes and may play a role in the pathogenesis of myelodysplastic syndromes (MDS). To clarify the possible association between genomic instability and clinical outcome in MDS patients, we compared telomere dynamics to the recently established International Prognostic Scoring System (IPSS) risk groups for MDS. We measured the terminal restriction fragments (TRFs) of 93 patients with MDS at the time of diagnosis, and telomerase activity was analyzed in 62 patients with MDS using the PCR-based telomeric repeat amplification protocol (TRAP) assay. A total of 53 of 93 MDS patients had TRFs within the age- matched normal range, and the remaining patients showed shortened TRFs (35 patients) or elongated TRFs (5 patients). MDS patients with shortened TRFs had a significantly low hemoglobin concentration (P = 0.04), a high percentage of marrow blasts (P = 0.02), and a high incidence of cytogenetic abnormalities (P < 0.05). The incidence of leukemic transformation was significantly high in patients with shortened TRF length (P < 0.05). In addition, patients with shortened TRF length were frequently seen in the IPSS high-risk group (P < 0.01). Most of the MDS patients had normal-to-low levels of telomerase activity, suggesting that changes in TRF length rather than telomerase activity may more accurately reflect the pathophysiology of MDS. MDS patients with shortened TRF length had a very poor prognosis (P < 0.01), suggesting that telomere dynamics may be linked to clinical outcome in MDS patients. Thus, an abnormal mechanism of telomere maintenance in subgroups of MDS patients may be an early indication of genomic instability. This study demonstrates that telomere stability is frequently impaired in a high-risk group of MDS patients and suggests that, in combination with the IPSS classification system, measurement of TRFs may be useful in the future to stratify MDS patients according to risk and manage the care of MDS patients.

Original languageEnglish (US)
Pages (from-to)1155-1160
Number of pages6
JournalClinical Cancer Research
Volume5
Issue number5
StatePublished - May 1999

Fingerprint

Myelodysplastic Syndromes
Telomere
Genomic Instability
Telomerase
Incidence
Chromosome Aberrations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ohyashiki, J. H., Iwama, H., Yahata, N., Ando, K., Hayashi, S., Shay, J. W., & Ohyashiki, K. (1999). Telomere stability is frequently impaired in high-risk groups of patients with myelodysplastic syndromes. Clinical Cancer Research, 5(5), 1155-1160.

Telomere stability is frequently impaired in high-risk groups of patients with myelodysplastic syndromes. / Ohyashiki, Junko H.; Iwama, Hiroshi; Yahata, Naoyuki; Ando, Keiko; Hayashi, Shigefumi; Shay, Jerry W.; Ohyashiki, Kazuma.

In: Clinical Cancer Research, Vol. 5, No. 5, 05.1999, p. 1155-1160.

Research output: Contribution to journalArticle

Ohyashiki, JH, Iwama, H, Yahata, N, Ando, K, Hayashi, S, Shay, JW & Ohyashiki, K 1999, 'Telomere stability is frequently impaired in high-risk groups of patients with myelodysplastic syndromes', Clinical Cancer Research, vol. 5, no. 5, pp. 1155-1160.
Ohyashiki, Junko H. ; Iwama, Hiroshi ; Yahata, Naoyuki ; Ando, Keiko ; Hayashi, Shigefumi ; Shay, Jerry W. ; Ohyashiki, Kazuma. / Telomere stability is frequently impaired in high-risk groups of patients with myelodysplastic syndromes. In: Clinical Cancer Research. 1999 ; Vol. 5, No. 5. pp. 1155-1160.
@article{c115fb92c9464dc8b49e8a52d0bfe4f1,
title = "Telomere stability is frequently impaired in high-risk groups of patients with myelodysplastic syndromes",
abstract = "Genomic instability induces an accumulation of genetic changes and may play a role in the pathogenesis of myelodysplastic syndromes (MDS). To clarify the possible association between genomic instability and clinical outcome in MDS patients, we compared telomere dynamics to the recently established International Prognostic Scoring System (IPSS) risk groups for MDS. We measured the terminal restriction fragments (TRFs) of 93 patients with MDS at the time of diagnosis, and telomerase activity was analyzed in 62 patients with MDS using the PCR-based telomeric repeat amplification protocol (TRAP) assay. A total of 53 of 93 MDS patients had TRFs within the age- matched normal range, and the remaining patients showed shortened TRFs (35 patients) or elongated TRFs (5 patients). MDS patients with shortened TRFs had a significantly low hemoglobin concentration (P = 0.04), a high percentage of marrow blasts (P = 0.02), and a high incidence of cytogenetic abnormalities (P < 0.05). The incidence of leukemic transformation was significantly high in patients with shortened TRF length (P < 0.05). In addition, patients with shortened TRF length were frequently seen in the IPSS high-risk group (P < 0.01). Most of the MDS patients had normal-to-low levels of telomerase activity, suggesting that changes in TRF length rather than telomerase activity may more accurately reflect the pathophysiology of MDS. MDS patients with shortened TRF length had a very poor prognosis (P < 0.01), suggesting that telomere dynamics may be linked to clinical outcome in MDS patients. Thus, an abnormal mechanism of telomere maintenance in subgroups of MDS patients may be an early indication of genomic instability. This study demonstrates that telomere stability is frequently impaired in a high-risk group of MDS patients and suggests that, in combination with the IPSS classification system, measurement of TRFs may be useful in the future to stratify MDS patients according to risk and manage the care of MDS patients.",
author = "Ohyashiki, {Junko H.} and Hiroshi Iwama and Naoyuki Yahata and Keiko Ando and Shigefumi Hayashi and Shay, {Jerry W.} and Kazuma Ohyashiki",
year = "1999",
month = "5",
language = "English (US)",
volume = "5",
pages = "1155--1160",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "5",

}

TY - JOUR

T1 - Telomere stability is frequently impaired in high-risk groups of patients with myelodysplastic syndromes

AU - Ohyashiki, Junko H.

AU - Iwama, Hiroshi

AU - Yahata, Naoyuki

AU - Ando, Keiko

AU - Hayashi, Shigefumi

AU - Shay, Jerry W.

AU - Ohyashiki, Kazuma

PY - 1999/5

Y1 - 1999/5

N2 - Genomic instability induces an accumulation of genetic changes and may play a role in the pathogenesis of myelodysplastic syndromes (MDS). To clarify the possible association between genomic instability and clinical outcome in MDS patients, we compared telomere dynamics to the recently established International Prognostic Scoring System (IPSS) risk groups for MDS. We measured the terminal restriction fragments (TRFs) of 93 patients with MDS at the time of diagnosis, and telomerase activity was analyzed in 62 patients with MDS using the PCR-based telomeric repeat amplification protocol (TRAP) assay. A total of 53 of 93 MDS patients had TRFs within the age- matched normal range, and the remaining patients showed shortened TRFs (35 patients) or elongated TRFs (5 patients). MDS patients with shortened TRFs had a significantly low hemoglobin concentration (P = 0.04), a high percentage of marrow blasts (P = 0.02), and a high incidence of cytogenetic abnormalities (P < 0.05). The incidence of leukemic transformation was significantly high in patients with shortened TRF length (P < 0.05). In addition, patients with shortened TRF length were frequently seen in the IPSS high-risk group (P < 0.01). Most of the MDS patients had normal-to-low levels of telomerase activity, suggesting that changes in TRF length rather than telomerase activity may more accurately reflect the pathophysiology of MDS. MDS patients with shortened TRF length had a very poor prognosis (P < 0.01), suggesting that telomere dynamics may be linked to clinical outcome in MDS patients. Thus, an abnormal mechanism of telomere maintenance in subgroups of MDS patients may be an early indication of genomic instability. This study demonstrates that telomere stability is frequently impaired in a high-risk group of MDS patients and suggests that, in combination with the IPSS classification system, measurement of TRFs may be useful in the future to stratify MDS patients according to risk and manage the care of MDS patients.

AB - Genomic instability induces an accumulation of genetic changes and may play a role in the pathogenesis of myelodysplastic syndromes (MDS). To clarify the possible association between genomic instability and clinical outcome in MDS patients, we compared telomere dynamics to the recently established International Prognostic Scoring System (IPSS) risk groups for MDS. We measured the terminal restriction fragments (TRFs) of 93 patients with MDS at the time of diagnosis, and telomerase activity was analyzed in 62 patients with MDS using the PCR-based telomeric repeat amplification protocol (TRAP) assay. A total of 53 of 93 MDS patients had TRFs within the age- matched normal range, and the remaining patients showed shortened TRFs (35 patients) or elongated TRFs (5 patients). MDS patients with shortened TRFs had a significantly low hemoglobin concentration (P = 0.04), a high percentage of marrow blasts (P = 0.02), and a high incidence of cytogenetic abnormalities (P < 0.05). The incidence of leukemic transformation was significantly high in patients with shortened TRF length (P < 0.05). In addition, patients with shortened TRF length were frequently seen in the IPSS high-risk group (P < 0.01). Most of the MDS patients had normal-to-low levels of telomerase activity, suggesting that changes in TRF length rather than telomerase activity may more accurately reflect the pathophysiology of MDS. MDS patients with shortened TRF length had a very poor prognosis (P < 0.01), suggesting that telomere dynamics may be linked to clinical outcome in MDS patients. Thus, an abnormal mechanism of telomere maintenance in subgroups of MDS patients may be an early indication of genomic instability. This study demonstrates that telomere stability is frequently impaired in a high-risk group of MDS patients and suggests that, in combination with the IPSS classification system, measurement of TRFs may be useful in the future to stratify MDS patients according to risk and manage the care of MDS patients.

UR - http://www.scopus.com/inward/record.url?scp=0032902504&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032902504&partnerID=8YFLogxK

M3 - Article

VL - 5

SP - 1155

EP - 1160

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 5

ER -