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hTERT promoter methylation and telomere length in childhood acute lymphoblastic leukemia: associations with immunophenotype and cytogenetic subgroup
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. (Alafuzoff)
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2011 (English)In: Experimental Hematology, ISSN 0301-472X, E-ISSN 1873-2399, Vol. 39, no 12, 1144-1151 p.Article in journal (Refereed) Published
Abstract [en]

Telomere maintenance, important for long-term cell survival and malignant transformation, is directed by a multitude of factors, including epigenetic mechanisms, and has been implicated in outcomes for patients with leukemia. In the present study, the objective was to investigate the biological and clinical significance of telomere length and promoter methylation of the human telomerase reverse transcriptase gene in childhood acute lymphoblastic leukemia. A cohort of 169 childhood acute lymphoblastic leukemias was investigated for telomere length, human telomerase reverse transcriptase gene promoter methylation status, genomic aberrations, immunophenotype, and clinical outcomes. Methylation of the core promoter of the human telomerase reverse transcriptase (hTERT) gene was demonstrated in 24% of diagnostic samples, with a significant difference between B-cell precursor (n = 130) and T-cell acute lymphoblastic leukemia (ALL) (n = 17) cases (18% and 72%, respectively; p < 0.001). No remission sample demonstrated hTERT promoter methylation (n = 40). Within the B-cell precursor group, t(12;21)(p13;q22) [ETV6/RUNX1] cases (n = 19) showed a much higher frequency of hTERT methylation than high-hyperdiploid (51 61 chromosomes) ALL (n = 44) (63% and 7%, respectively; p < 0.001). hTERT messenger RNA levels were negatively associated with methylation status and, in the t(12;21) group, methylated cases had shorter telomeres (p = 0.017). In low-risk B-cell precursor patients (n = 101), long telomeres indicated a worse prognosis. The collected data from the present study indicate that the telomere biology in childhood ALL has clinical implications and reflects molecular differences between diverse ALL subgroups.

Place, publisher, year, edition, pages
2011. Vol. 39, no 12, 1144-1151 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-165630DOI: 10.1016/j.exphem.2011.08.014ISI: 000297566500005OAI: oai:DiVA.org:uu-165630DiVA: diva2:475182
Available from: 2012-01-10 Created: 2012-01-09 Last updated: 2012-01-17Bibliographically approved

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