Flow cytometric detection of accelerated telomere shortening in myelodysplastic syndromes: correlations with aetiological and clinical-biological findings

Eur J Haematol. 2004 Nov;73(5):351-8. doi: 10.1111/j.1600-0609.2004.00305.x.

Abstract

Using quantitative fluorescence in situ hybridisation and flow cytometry (flow-FISH), we investigated the biological and clinical relevance of telomere length in 55 patients affected by myelodysplastic syndromes (MDS) compared with 55 sex- and age-matched controls. We found that telomere fluorescence in MDS granulocytes, and CD34+ cells did not decline with age as in normal controls and that MDS granulocytes and CD34+ cells had significantly shorter telomeres than healthy controls. A significant higher incidence of cases with intermediate-unfavourable cytogenetics and International Prognostic Scoring System (IPSS) int-2/high-risk group was observed among patients with lower telomere fluorescence. We also found that apoptosis in CD34+ cells was significantly higher in IPSS int-1 low-risk patients when compared with IPSS int-2 high-risk cases and healthy controls and that CD34+ cell telomere fluorescence directly correlated with CD34+ cell apoptosis. Reduced telomere fluorescence was associated with a history of occupational exposure to toxic agents and with worse survival in univariate and multivariate analyses. Our results suggest that flow-cytometry assessment of telomere dynamics may represent a valuable tool in the biological and clinical-prognostic characterisation of MDS disorders.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anemia, Refractory / blood
  • Anemia, Refractory, with Excess of Blasts / blood
  • Antigens, CD34 / analysis
  • Apoptosis
  • Chromosomes, Human, Pair 19
  • Chromosomes, Human, Pair 5
  • Chromosomes, Human, Pair 8
  • Chromosomes, Human, Y
  • Female
  • Flow Cytometry* / methods
  • Gene Deletion
  • Granulocytes / ultrastructure
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, Myelomonocytic, Chronic / blood
  • Male
  • Middle Aged
  • Monosomy
  • Myelodysplastic Syndromes / blood*
  • Myelodysplastic Syndromes / etiology
  • Myelodysplastic Syndromes / genetics
  • Pesticides / toxicity
  • Prognosis
  • Solvents / toxicity
  • Survival Rate
  • Telomere / ultrastructure*
  • Trisomy

Substances

  • Antigens, CD34
  • Pesticides
  • Solvents