Telomerase Activity and Expression and Telomere Analysis in Situ in the Course of Treatment of Childhood Leukemias

Maláska, Jan; Skleničková, Marie; Krejčı́, Kateřina; Fajkusová, Lenka; Bajer, Milan; Hrstková, Hana; Fajkus, Jiřı́

doi:10.1006/bcmd.2000.0332

Cited by 15 publications

(14 citation statements)

References 11 publications

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“…Up-regulation of the enzyme telomerase is found in over 85% of human cancers, 32 and overexpression is commonly found in leukemic cell lines and in peripheral blood and bone marrow samples of patients with leukemia. 30,[33][34][35][36][37][38] Upon treatment, telomerase activity reportedly decreases, due to either the elimination of the leukemic clone by cytotoxic agents 30,35 and/or to enzyme down-regulation by noncytotoxic differentiating agents. 37 Furthermore, persistence of elevated levels of telomerase during remission has been associated with relapse in two patients with ALL, 38 pointing to telomerase as a marker of residual disease.…”

Section: Introductionmentioning

confidence: 99%

Telomere dynamics in childhood leukemia and solid tumors: a follow-up study

et al. 2003

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Telomeres of hematopoietic cells shorten with age, possibly contributing to the aging-associated hematopoietic pathology (immunosenescence, malignant transformation). Accelerated telomere shortening is seen with replicative stress, such as during administration of serial chemotherapy cycles for the treatment of childhood cancer. To define the long-term consequences of pediatric cancer treatment on hematopoietic cell telomere length, we undertook a prospective 4-year follow-up study of a 61-patient cohort of pediatric malignancies in a community-based setting. We found that mononuclear cells (MNC) and granulocytes of children with standard-risk acute lymphoblastic leukemia (ALL) suffered minimal telomere shortening throughout therapy (less than 1 kbp; average follow-up, 20 months), while those of children with solid tumors showed greater and more heterogenous telomere attrition (0.5-2.8 kbp, average follow-up, 9 months). In addition, we evaluated the role of telomerase, the enzyme commonly up-regulated in pediatric leukemic and solid tumor cells for telomere length maintenance, as a disease marker. Serial determinations of telomerase in MNC were useful to confirm disease remission in leukemia, but play no role in the follow-up of children with solid tumors.

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Section: Introductionmentioning

confidence: 99%

Telomere dynamics in childhood leukemia and solid tumors: a follow-up study

et al. 2003

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“…Three studies investigated TA during the course of disease and correlations between enzyme activity and response to therapy were found. [4][5][6] Likewise, a reduction of telomere length could be observed during treatment. 4,5 Our results indicate that longitudinal analysis of TA and TRF in long-term studies would be needed to investigate the impact of changes in TA and telomere length during course of disease and its treatment in children with T-ALL.…”

Section: Telomeres and Telomerase In Paediatric Patients With T-cell mentioning

confidence: 91%

“…Our results are in agreement with previous reports, which showed a general association between TA and expression of hTERT in samples of children with acute leukaemia. 6,8 Any discordance between expression of hTERT and TA (as seen best in patient no. 11) might be most likely explained by transcriptional regulation of hTERT.…”

Section: Telomeres and Telomerase In Paediatric Patients With T-cell mentioning

confidence: 99%

“…Our findings are consistent with previous reports, which showed high levels of TA in samples of children with acute leukaemia compared to healthy individuals. 4,6,8 Normalized expression of hTERT was measured at the mRNA level by real-time TaqMan s PCR as described recently. 11 Nonactivated PBMCs obtained from a second healthy young adult served as control.…”

Section: Telomeres and Telomerase In Paediatric Patients With T-cell mentioning

confidence: 99%

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

et al. 2004

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“…Southern blot [44,45] Modified SB Slot blot [46] [ 47] Hybridization protection assay [48] Fluorescence in situ hybridization [50] PNA Flow cytometry-FISH [58][59][60][61][62][63][64] Modified flow-FISH Multicolor flow-FISH [62,65] [ 66] Primed in situ [67][68][69][70] Dideoxy-PRINS Double strand-PRINS [71,72] [73]…”

Section: Modifications Referencesmentioning

confidence: 99%

The telomere length dynamic and methods of its assessment

Lin

Yan

2005

J Cellular Mol Med

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Human telomeres are composed of long repeating sequences of TTAGGG, associated with a variety of telomere‐binding proteins. Its function as an end‐protector of chromosomes prevents the chromosome from end‐to‐end fusion, recombination and degradation. Telomerase acts as reverse transcriptase in the elongation of telomeres, which prevent the loss of telomeres due to the end replication problems. However, telomerase activity is detected at low level in somatic cells and high level in embryonic stem cells and tumor cells. It confers immortality to embryonic stem cells and tumor cells. In most tumor cells, telomeres are extremely short and stable. Telomere length is an important indicator of the telomerase activity in tumor cells and it may be used in the prognosis of malignancy. Thus, the assessment of telomeres length is of great experimental and clinical significance. This review describes the role of telomere and telomerase in cancer pathogenesis and the dynamics of the telomeres length in different cell types. The various methods of measurement of telomeres length, i.e. southern blot, hybridization protection assay, fluorescence in situ hybridization, primed in situ, quantitative PCR and single telomere length analysis are discussed. The principle and comparative evaluation of these methods are reviewed. The detection of G‐strand overhang by telomeric‐oligonucleotide ligation assay, primer extension/nick translation assay and electron microscopy are briefly discussed.

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Telomerase Activity and Expression and Telomere Analysis in Situ in the Course of Treatment of Childhood Leukemias

Cited by 15 publications

References 11 publications

Telomere dynamics in childhood leukemia and solid tumors: a follow-up study

Telomere dynamics in childhood leukemia and solid tumors: a follow-up study

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

The telomere length dynamic and methods of its assessment

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