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.
Section of Haematology, Department of Biomedical Sciences, University of Ferrara, Ferrara, Italy. rglgmt@unife.it
Gian Matteo
GM
Rigolin
Matteo Della
MD
Porta
Anna Maria
AM
Bugli
Barbara
B
Castagnari
Endri
E
Mauro
Letizia Zenone
LZ
Bragotti
Maria
M
Ciccone
Antonio
A
Cuneo
Gianluigi
G
Castoldi
D000368:Aged; D000369:Aged, 80 and over; D000753:Anemia, Refractory / Q000097:blood; D000754:Anemia, Refractory, with Excess of Blasts / Q000097:blood; D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis; D002888:Chromosomes, Human, Pair 19; D002895:Chromosomes, Human, Pair 5; D002898:Chromosomes, Human, Pair 8; D041322:Chromosomes, Human, Y; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D017353:Gene Deletion; D006098:Granulocytes / Q000648:ultrastructure; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015477:Leukemia, Myelomonocytic, Chronic / Q000097:blood; D008297:Male; D008875:Middle Aged; D009006:Monosomy; D009190:Myelodysplastic Syndromes / Q000097:blood* / Q000209:etiology / Q000235:genetics; D010575:Pesticides / Q000633:toxicity; D011379:Prognosis; D012997:Solvents / Q000633:toxicity; D015996:Survival Rate; D016615:Telomere / Q000648:ultrastructure*; D014314:Trisomy
D018952:Antigens, CD34; D010575:Pesticides; D012997:Solvents