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

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.