TY - JOUR
T1 - Increase of telomerase activity and hTERT expression in myelodysplastic syndromes
AU - Briatore, Federica
AU - Barrera, Giuseppina
AU - Pizzimenti, Stefania
AU - Toaldo, Cristina
AU - Della Casa, Chiara
AU - Laurora, Stefano
AU - Pettazzoni, Piergiorgio
AU - Dianzani, Mario Umberto
AU - Ferrero, Dario
N1 - Funding Information:
This work was supported by grants from Università di Torino and Regione Piemonte.
PY - 2009/5/15
Y1 - 2009/5/15
N2 - Telomerase enzyme, containing a catalytic subunit, the human telomerase reverse transcriptase (hTERT), and a small integral RNA component, synthesises the telomeres, the ends of eukaryotic chromosomes. Inhibition of telomerase activity leads the cells to senescence and death. Myelodysplastic syndromes (MSD) are hematological malignancies characterized by peripheral blood cytopenia and ineffective hematopoiesis. Telomerase activity and hTERT expression in MDS patients were independently investigated by different groups obtaining contradictory results. We analyzed telomerase activity and hTERT expression in the bone marrow of ten control, 15 MDS patients and two patients with AML, likely evolved from a previous MDS. Moreover, the expression of c-myc, mad1, p53 (transcription factors involved in hTERT expression regulation), has been investigated. Telomerase activity and hTERT expression increased in the MDS patients with respect to the controls. The analysis of the MDS subgroups, indicated that patients with more severe disease demonstrated significantly higher levels of hTERT expression and telomerase activity with respect to the patients with more favorable disease. c-Myc and p53 expressions were not significantly different between controls and MDS patients, whereas mad1 expression was increased in MDS patiens, particularly in those with more favorable disease. We hypothesize that mad1 increase can contribute to reduce the hTERT expression in the early stage of disease and we suggest that hTERT expression and telomerase activity, whether confirmed in larger series of cases could support other parameters in the diagnosis and stadiation of MDS.
AB - Telomerase enzyme, containing a catalytic subunit, the human telomerase reverse transcriptase (hTERT), and a small integral RNA component, synthesises the telomeres, the ends of eukaryotic chromosomes. Inhibition of telomerase activity leads the cells to senescence and death. Myelodysplastic syndromes (MSD) are hematological malignancies characterized by peripheral blood cytopenia and ineffective hematopoiesis. Telomerase activity and hTERT expression in MDS patients were independently investigated by different groups obtaining contradictory results. We analyzed telomerase activity and hTERT expression in the bone marrow of ten control, 15 MDS patients and two patients with AML, likely evolved from a previous MDS. Moreover, the expression of c-myc, mad1, p53 (transcription factors involved in hTERT expression regulation), has been investigated. Telomerase activity and hTERT expression increased in the MDS patients with respect to the controls. The analysis of the MDS subgroups, indicated that patients with more severe disease demonstrated significantly higher levels of hTERT expression and telomerase activity with respect to the patients with more favorable disease. c-Myc and p53 expressions were not significantly different between controls and MDS patients, whereas mad1 expression was increased in MDS patiens, particularly in those with more favorable disease. We hypothesize that mad1 increase can contribute to reduce the hTERT expression in the early stage of disease and we suggest that hTERT expression and telomerase activity, whether confirmed in larger series of cases could support other parameters in the diagnosis and stadiation of MDS.
KW - Myelodysplastic syndromes
KW - Telomerase activity
KW - Transcription factors
KW - hTERT
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U2 - 10.4161/cbt.8.10.8130
DO - 10.4161/cbt.8.10.8130
M3 - Article
C2 - 19270495
AN - SCOPUS:68049129840
SN - 1538-4047
VL - 8
SP - 883
EP - 889
JO - Cancer Biology and Therapy
JF - Cancer Biology and Therapy
IS - 10
ER -