Telomere shortening and chromosomal instability in myelodysplastic syndromes.
Telomere shortening and chromosomal instability are believed to play an important role in the development of myeloid neoplasia. So far, published data are only available on the average telomere length in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), but not on the telomere length of individual chromosomes. We used a new technique, telomere/centromere-fluorescence in situ hybridization (T/C-FISH), which combines fluorescence R-banding and FISH using a probe against the telomere repeats to measure the telomere length of each chromosome arm in 78 patients with MDS. In line with the previous results, patients with MDS showed significantly shorter telomeres than those of healthy controls. Telomere lengths did not differ significantly between distinct morphological subtypes of MDS. However, there was a significant difference in telomere length between patients with an isolated monosomy 7 and patients with a normal karyotype (P < 0.05). Notably, patients with an isolated monosomy 7 showed significantly longer telomeres than patients with a normal karyotype in many chromosome arms, among them 7p and 7q. Neo-telomeres were found in two patients with a complex karyotype, in one case at the fusion site of a dic(14;20). Normal and aberrant metaphases of the same patient did not differ in telomere length, thus indicating to telomere shortening as a basic mechanism affecting all hematopoietic cells in patients with MDS. In some MDS subtypes, like MDS with isolated monosomy 7, telomeres may be stabilized and even increase in length because of the activation of telomerase or alternative mechanisms.
Lange
Kathrin
K
Institute of Cell and Molecular Pathology, Hannover Medical School, Germany.
Holm
Lisa
L
Vang Nielsen
Kirsten
K
Hahn
Andreas
A
Hofmann
Winfried
W
Kreipe
Hans
H
Schlegelberger
Brigitte
B
Göhring
Gudrun
G
D000740:Anemia / Q000235:genetics; D043171:Chromosomal Instability / Q000235:genetics*; D002871:Chromosome Banding / Q000379:methods; D002897:Chromosomes, Human, Pair 7; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008677:Metaphase / Q000235:genetics; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D012016:Reference Values; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics* / Q000648:ultrastructure
D019098:Telomerase