Telomere length and hTERT expression in patients with acute myeloid leukemia correlates with chromosomal abnormalities.
OBJECTIVE
Acute myeloid leukemia (AML) is a malignant, genetically heterogenous disorder characterized by uncontrolled growth of immature myeloid cells. The aim of this study was to analyze whether telomere length and/or hTERT expression are correlated with clonal chromosomal aberrations in AML.


METHODS
Telomere length in mononuclear cells derived from 137 previously untreated patients with >or= 80% blasts was analyzed by flow fluorescent in situ hybridization. Results were expressed in telomere fluorescence Units (1 TFU=1 kb). The expression of hTERT, including its different splice variants was studied by reverse transcription-polymerase chain reaction.


RESULTS
Age-adjusted telomere length in AML patients was significantly reduced as compared to in matched controls, consisting of peripheral blood granulocytes from healthy individuals (0-90 years) (median: -2.5 TFU; p<0.001). Patients with an aberrant karyotype had significantly shorter telomeres than patients with a normal karyotype (median -3.0 vs. -2.3 TFU; p=0.03). The shortest telomeres were found in patients with multiple aberrations (median -3.7 TFU; p=0.03). hTERT expression was found to be correlated with chromosomal abnormalities as well as with the detection of functional hTERT splicing variants.


CONCLUSIONS
These findings suggest an important role of intense telomere loss in the development of genetic instability during the pathogenesis of AML. It is assumed that critical telomere shortening in AML blasts could lead to telomerase activation and therefore prevent blasts from replicative senescence, one possible mechanism for clonal selection and disease progression. Therefore, telomere length might serve as a prognostic marker for AML patients. These findings would have to be confirmed in large, prospective studies.
Hartmann
Ulrike
U
Dept. of Hematology and Oncology, University of Tübingen, Germany.
Brümmendorf
Tim H
TH
Balabanov
Stefan
S
Thiede
Christian
C
Illme
Thomas
T
Schaich
Markus
M
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007951:Leukemia, Myeloid / Q000209:etiology / Q000235:genetics*; D008875:Middle Aged; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000648:ultrastructure*
D019098:Telomerase