Telomerase activity in myelodysplastic syndromes

Gürkan, Emel; Tanrıverdi, Kahraman; Başlamışlı, Fikri

doi:10.1016/j.leukres.2005.03.006

Cited by 31 publications

(23 citation statements)

References 14 publications

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“…On the contrary Campbell et al 35 recently reported that hTERT is downregulated in the hematopoietic stem cells of patients with chronic myeloid leukaemia. Oshima K, et al 36 found that telomerase activity is higher in AML/MDS than in MDS and controls, whereas opposite results were reported by other authors 16 that did not find significant differences in telomerase activity in bone marrow of MDS patients compared to controls. It must be remarked that in literature data telomerase activity and hTERT expression were independently investigated by different groups in MDS patients, and this may account for some discrepancies in reported results.…”

Section: Discussionmentioning

confidence: 81%

“…15 It has been suggested that telomerase activity and hTERT expression may be prognostically important in patients with MDS. 16,17 However, a contemporary analysis of telomerase activity and hTERT expression in MSD patients has not yet been performed. Regulation of hTERT expression depends on different transcription factors that bind hTERT promoter 18 and positively or negatively control hTERT expression.…”

Section: Introductionmentioning

confidence: 99%

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Increase of telomerase activity and hTERT expression in myelodysplastic syndromes

Briatore¹,

Barrera²,

Pizzimenti³

et al. 2009

Cancer Biology & Therapy

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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.

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Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Increase of telomerase activity and hTERT expression in myelodysplastic syndromes

Briatore¹,

Barrera²,

Pizzimenti³

et al. 2009

Cancer Biology & Therapy

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show abstract

“…Significant numbers of patients with MDS will progress to AML. TL is reduced in a proportion of MDS patients (Ohyashiki et al, 1999;Rigolin et al, 2004;Sieglova et al, 2004) and TA is also increased in a proportion of MDS patients (Ohyashiki et al, 1999;Gurkan et al, 2005). Short telomeres were inversely associated with marrow blasts, genomic-rearrangements and high risk International Prognostic Scoring System (IPSS) scores (Ohyashiki et al, 1999) but no such association was demonstrated with TA (Gurkan et al, 2005).…”

Section: Bone Marrow Failure Syndromes and Myelodysplasiamentioning

confidence: 99%

“…TL is reduced in a proportion of MDS patients (Ohyashiki et al, 1999;Rigolin et al, 2004;Sieglova et al, 2004) and TA is also increased in a proportion of MDS patients (Ohyashiki et al, 1999;Gurkan et al, 2005). Short telomeres were inversely associated with marrow blasts, genomic-rearrangements and high risk International Prognostic Scoring System (IPSS) scores (Ohyashiki et al, 1999) but no such association was demonstrated with TA (Gurkan et al, 2005). TL has been shown to decrease in patients who have undergone chemotherapy and a subset of patients with lymphoma who have undergone autologous transplantation have been shown to have shortened TL and increased risk of developing MDS and AML (Chakraborty et al, 2009).…”

Section: Bone Marrow Failure Syndromes and Myelodysplasiamentioning

confidence: 99%

Telomere dysfunction and its role in haematological cancer

Jones¹,

Pepper²,

Baird

2012

Br J Haematol

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SummaryObservations in human tumours, as well as mouse models, have indicated that telomere dysfunction may be a key event driving genomic instability and disease progression in many solid tumour types. In this scenario, telomere shortening ultimately results in telomere dysfunction, fusion and genomic instability, creating the large-scale rearrangements that are characteristic of these tumours. It is now becoming apparent that this paradigm may also apply to haematological malignancies; indeed these conditions have provided some of the most convincing evidence of telomere dysfunction in any malignancy. Telomere length has been shown in several malignancies to provide clinically useful prognostic information, implicating telomere dysfunction in disease progression. In these malignancies extreme telomere shortening, telomere dysfunction and fusion have all been documented and correlate with the emergence of increased genomic complexity. Telomeres may therefore represent both a clinically useful prognostic tool and a potential target for therapeutic intervention.

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“…Increased telomerase activity has been reported in approximately 40% of MDS patients, but correlations with outcome or telomere length have been inconsistent (Engelhardt et al 2004;Gurkan et al 2005;Ohyashiki et al 1994;Ohyashiki et al 1999). MDS appears to be in the pathway of progression from BMF (acquired AA or an IBMFS) to leukemia.…”

Section: Myelodysplastic Syndromementioning

confidence: 99%

The role of telomere biology in bone marrow failure and other disorders

Savage

Alter

2008

Mechanisms of Ageing and Development

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Telomeres, consisting of nucleotide repeats and a protein complex at chromosome ends, are essential in maintaining chromosomal integrity. Dyskeratosis congenita (DC) is the inherited bone marrow failure syndrome (IBMFS) that epitomizes the effects of abnormal telomere biology. Patients with DC have extremely short telomere lengths (<1 st percentile) and many have mutations in telomere biology genes. Interpretation of telomere length in other IBMFSs is less straightforward. Abnormal telomere shortening has been reported in patients with apparently acquired hematologic disorders, including aplastic anemia, myeolodysplasia, paroxysmal nocturnal hemoglobinuria, and leukemia. In these disorders, the shortest lived cells have the shortest telomeres, suggestive of increased hematopoietic stress. Telomeres are also markers of replicative and/or oxidative stress in other complex disease pathways, such as inflammation, stress, and carcinogenesis.The spectrum of related disorders caused by mutations in telomere biology genes extends beyond classical DC to include marrow failure that does not respond to immunosuppression, idiopathic pulmonary fibrosis, and possibly other syndromes. We suggest that such patients are categorized as having an inherited disorder of telomere biology. Longitudinal studies of patients with very short telomeres but without classical DC are necessary to further understand the long-term sequelae, such as malignancy, osteonecrosis/osteoporosis, and pulmonary and liver disease.

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Telomerase activity in myelodysplastic syndromes

Cited by 31 publications

References 14 publications

Increase of telomerase activity and hTERT expression in myelodysplastic syndromes

Increase of telomerase activity and hTERT expression in myelodysplastic syndromes

Telomere dysfunction and its role in haematological cancer

The role of telomere biology in bone marrow failure and other disorders

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