Telomeres and telomerase in paediatric patients with T-cell acute lymphoblastic leukaemia (T-ALL)

Kleideiter, Elke; Bangerter, U.; Schwab, Matthias; Boukamp, Petra; Kościelniak, Ewa; Klotz, Ulrich; Greil, Johann

doi:10.1038/sj.leu.2403596

Cited by 14 publications

(9 citation statements)

References 11 publications

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“…In contrast Ohyashiki et al found no correlation between telomerase activity and survival for adult patients with acute myeloid leukemia (10). For children with acute lymphoblastic leukemia telomerase activity was not associated with clinical outcome (25). In patients who achieved remission telomerase activity levels decreased to normal but were significantly higher at the time of recurrence or disease progression compared with telomerase activity levels at the time of diagnosis (9,10,12).…”

Section: Discussionmentioning

confidence: 87%

Telomerase activity in peripheral blood mononuclear cells after whole body irradiation

Neuhof

Bischof²,

Debus³

et al. 2007

Oncol Rep

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Telomerase activity in vitro represents a radiationinducible function. To test this effect after irradiation in vivo, we measured telomerase activity in peripheral blood mononuclear cells (PBMC) of 25 patients with leukemia or lymphoma before and 1 h after whole body irradiation. Telomerase activity of the patients was compared to telomerase activity in PBMC of 15 healthy volunteers. Peripheral blood of the patients was taken before and 1 h after the first fraction of whole body irradiation (2 Gy). Blood samples of the volunteers were irradiated ex vivo with 2 Gy. After Ficoll-Paque density gradient centrifugation telomerase activity of 10 4 PBMC per sample was measured using the telomerase PCR ELISA method. No age-dependence of telomerase activity was detected for both the volunteer and the patient group. Telomerase activity in patients was not statistically significantly increased compared to healthy individuals, and this parameter was also no prognostic factor for patient survival. After whole body irradiation an induction of telomerase activity was observed for only 7 patients (28%), or in PBMC of 2 volunteers (13%), respectively. In patients with radiation-inducible telomerase activity, a slightly better survival was indicated, but this difference did not reach statistical significance. The feasibility to assess in vivo radiation-induction of telomerase activity in PBMC of leukemia or lymphoma patients was demonstrated. An unexpectedly low number of whole body irradiated patients displayed this phenotype, and the treatment impact of telomerase upregulation in PBMC upon radiation exposure needs to be further analyzed.

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Section: Discussionmentioning

confidence: 87%

Telomerase activity in peripheral blood mononuclear cells after whole body irradiation

Neuhof

Bischof²,

Debus³

et al. 2007

Oncol Rep

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“…A study of adult T-cell leukemia suggested that patients with elevated telomerase activity and shorter telomeres were more likely to have a poorer prognosis (Kubuki et al 2005). However, a study of pediatric T-cell leukemia did not find a relationship between telomerase activity or telomere length and outcome (Kleideiter et al 2005). …”

Section: Hematopoietic Malignanciesmentioning

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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“…In contrast, no relationship between hTERT expression, telomerase activity and telomere length in leukemic cells from paediatric patients with T-ALL and the clinical outcome or prognosis have been found in a study on 20 patients [87].…”

Section: Acute Leukemiamentioning

confidence: 89%

Diagnostics, Prognostic and Therapeutic Exploitation of Telomeres and Telomerase in Leukemias

Deville

Hillion²,

Lanotte³

et al. 2006

CPB

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Telomeres are specialized structures at the end of human chromosomes. Telomere length decreases with each cell division, thus, reflecting the mitotic history of somatic cells. Telomerase, the ribonucleoprotein enzyme which maintains telomeres of eukaryotic chromosomes, is up-regulated in the vast majority of human neoplasia but not in normal somatic tissues. In contrast to other somatic cells, normal primitive human hematopoietic cells and some peripheral blood cells expressed low levels of telomerase activity. This activity is thought to play an important role in self-renewal of hematopoietic stem cells. In malignant disorders, telomere lengths are generally shortened and telomerase expression and activity enhanced with high differences in the levels. Although it is necessary to be cautious in interpreting these data, there are indications that telomere length and telomerase expression and activity can serve as a molecular marker of the clinical progression and prognosis of most leukemias. Approaches that directly target telomerase, telomeres or telomerase regulatory mechanisms have been developed. Some of these anti-telomerase strategies in combination with conventional drugs proved to be promising in some types of leukemias.

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Telomeres and telomerase in paediatric patients with T-cell acute lymphoblastic leukaemia (T-ALL)

Cited by 14 publications

References 11 publications

Telomerase activity in peripheral blood mononuclear cells after whole body irradiation

Telomerase activity in peripheral blood mononuclear cells after whole body irradiation

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

Diagnostics, Prognostic and Therapeutic Exploitation of Telomeres and Telomerase in Leukemias

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