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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2013

Open Access 01-12-2013 | Short report

Presence of alternative lengthening of telomeres associated circular extrachromosome telomere repeats in primary leukemia cells of chronic myeloid leukemia

Authors: Oumar Samassekou, Abba Malina, Josée Hébert, Ju Yan

Published in: Journal of Hematology & Oncology | Issue 1/2013

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Abstract

Background

The predominant mechanism by which human tumors maintain telomere length is via telomerase. In ~10% of tumor samples, however, telomere length is conserved, despite no detectable telomerase activity, in part through activation of the alternative lengthening of telomeres (ALT) pathway.

Methods

We studied the circular extra-chromosomal telomeric repeat (ECTR), an ALT hallmark, and telomerase activity in 24 chronic myeloid leukemia (CML) patients in chronic phase (CP).

Results

We identified the presence of ECTR in primary leukemia cells from some of these samples, which indicates the possible involvement of an ALT mechanism. Moreover, we found that some samples exhibited both circular ECTR and telomerase activities, suggesting that both mechanisms can contribute to the onset of CML.

Conclusion

We propose that ALT or the combined activities of ALT and telomerase might be required for the early stages of leukemogenesis. These findings shed new light into the oncogenic pathways responsible for the maintenance of telomere length in leukemia, which will ultimately determine the effectiveness of anti-telomerase-based treatment protocols.
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Literature
1.
Zakian VA: Telomeres: beginning to understand the end. Science. 1995, 270: 1601-1607. 10.1126/science.270.5242.1601.CrossRefPubMed
2.
Henson JD, Cao Y, Huschtscha LI, Chang AC, Au AY, Pickett HA, Reddel RR: DNA C-circles are specific and quantifiable markers of alternative-lengthening-of-telomeres activity. Nat Biotechnol. 2009, 27: 1181-1185. 10.1038/nbt.1587.CrossRefPubMed
3.
Bryan TM, Englezou A, Dalla-Pozza L, Dunham MA, Reddel RR: Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nat Med. 1997, 3: 1271-1274. 10.1038/nm1197-1271.CrossRefPubMed
4.
Yeager TR, Neumann AA, Englezou A, Huschtscha LI, Noble JR, Reddel RR: Telomerase-negative immortalized human cells contain a novel type of promyelocytic leukemia (PML) body. Cancer Res. 1999, 59: 4175-4179.PubMed
5.
Cesare AJ, Reddel RR: Telomere uncapping and alternative lengthening of telomeres. Mech Ageing Dev. 2008, 129: 99-108. 10.1016/j.mad.2007.11.006.CrossRefPubMed
6.
Nabetani A, Ishikawa F: Alternative lengthening of telomeres pathway: recombination-mediated telomere maintenance mechanism in human cells. J Biochem. 2011, 149: 5-14. 10.1093/jb/mvq119.CrossRefPubMed
7.
Cesare AJ, Griffith JD: Telomeric DNA in ALT cells is characterized by free telomeric circles and heterogeneous t-loops. Mol Cell Biol. 2004, 24: 9948-9957. 10.1128/MCB.24.22.9948-9957.2004.PubMedCentralCrossRefPubMed
8.
Fasching CL, Neumann AA, Muntoni A, Yeager TR, Reddel RR: DNA damage induces alternative lengthening of telomeres (ALT) associated promyelocytic leukemia bodies that preferentially associate with linear telomeric DNA. Cancer Res. 2007, 67: 7072-7077. 10.1158/0008-5472.CAN-07-1556.CrossRefPubMed
9.
Pickett HA, Cesare AJ, Johnston RL, Neumann AA, Reddel RR: Control of telomere length by a trimming mechanism that involves generation of t-circles. EMBO J. 2009, 28: 799-809. 10.1038/emboj.2009.42.PubMedCentralCrossRefPubMed
10.
Wang RC, Smogorzewska A, de Lange T: Homologous recombination generates T-loop-sized deletions at human telomeres. Cell. 2004, 119: 355-10.1016/j.cell.2004.10.011.CrossRefPubMed
11.
de Klein A, van Kessel AG, Grosveld G, Bartram CR, Hagemeijer A, Bootsma D, Spurr NK, Heisterkamp N, Groffen J, Stephenson JR: A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia. Nature. 1982, 300: 765-767. 10.1038/300765a0.CrossRefPubMed
12.
Drummond M, Lennard A, Brummendorf T, Holyoake T: Telomere shortening correlates with prognostic score at diagnosis and proceeds rapidly during progression of chronic myeloid leukemia. Leuk Lymphoma. 2004, 45: 1775-1781. 10.1080/10428190410001693542.CrossRefPubMed
13.
Ohyashiki JH, Sashida G, Tauchi T, Ohyashiki K: Telomeres and telomerase in hematologic neoplasia. Oncogene. 2002, 21: 680-687. 10.1038/sj.onc.1205075.CrossRefPubMed
14.
15.
Tokutake Y, Matsumoto T, Watanabe T, Maeda S, Tahara H, Sakamoto S, Niida H, Sugimoto M, Ide T, Furuichi Y: Extra-chromosomal telomere repeat DNA in telomerase-negative immortalized cell lines. Biochem Biophys Res Commun. 1998, 247: 765-772. 10.1006/bbrc.1998.8876.CrossRefPubMed
16.
Costa A, Daidone MG, Daprai L, Villa R, Cantu S, Pilotti S, Mariani L, Gronchi A, Henson JD, Reddel RR, Zaffaroni N: Telomere maintenance mechanisms in liposarcomas: association with histologic subtypes and disease progression. Cancer Res. 2006, 66: 8918-8924. 10.1158/0008-5472.CAN-06-0273.CrossRefPubMed
17.
Villa R, Daidone MG, Motta R, Venturini L, De Marco C, Vannelli A, Kusamura S, Baratti D, Deraco M, Costa A: Multiple mechanisms of telomere maintenance exist and differentially affect clinical outcome in diffuse malignant peritoneal mesothelioma. Clin Cancer Res. 2008, 14: 4134-4140. 10.1158/1078-0432.CCR-08-0099.CrossRefPubMed
18.
Morrish TA, Greider CW: Short telomeres initiate telomere recombination in primary and tumor cells. PLoS Genet. 2009, 5: e1000357-10.1371/journal.pgen.1000357.PubMedCentralCrossRefPubMed
19.
Lau LM, Dagg RA, Henson JD, Au AY, Royds JA, Reddel RR: Detection of alternative lengthening of telomeres by telomere quantitative PCR. Nucleic Acids Res. 2013, 41: e34-10.1093/nar/gks781.PubMedCentralCrossRefPubMed
20.
Neumann AA, Watson CM, Noble JR, Pickett HA, Tam PP, Reddel RR: Alternative lengthening of telomeres in normal mammalian somatic cells. Genes Dev. 2013, 27: 18-23. 10.1101/gad.205062.112.PubMedCentralCrossRefPubMed
21.
Cerone MA, Autexier C, Londono-Vallejo JA, Bacchetti S: A human cell line that maintains telomeres in the absence of telomerase and of key markers of ALT. Oncogene. 2005, 24: 7893-7901. 10.1038/sj.onc.1208934.CrossRefPubMed
22.
Chen Q, Ijpma A, Greider CW: Two survivor pathways that allow growth in the absence of telomerase are generated by distinct telomere recombination events. Mol Cell Biol. 2001, 21: 1819-1827. 10.1128/MCB.21.5.1819-1827.2001.PubMedCentralCrossRefPubMed
23.
Samassekou O, Li H, Hébert J, Ntwari A, Wang H, Cliche CG, Bouchard E, Huang S, Yan J: Chromosome-arm-specific long telomeres: a new clonal event in primary chronic myelogenous leukemia cells. Neoplasia. 2011, 13: 550-560.PubMedCentralCrossRefPubMed
24.
Ohyashiki K, Ohyashiki JH, Iwama H, Hayashi S, Shay JW, Toyama K: Telomerase activity and cytogenetic changes in chronic myeloid leukemia with disease progression. Leukemia. 1997, 11: 190-194. 10.1038/sj.leu.2400560.CrossRefPubMed
Metadata
Title
Presence of alternative lengthening of telomeres associated circular extrachromosome telomere repeats in primary leukemia cells of chronic myeloid leukemia
Authors
Oumar Samassekou
Abba Malina
Josée Hébert
Ju Yan
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2013
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/1756-8722-6-26

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