title: Presence of alternative lengthening of telomeres associated circular extrachromosome telomere repeats in primary leukemia cells of chronic myeloid leukemia.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Oumar
authors.initials: O
authors.lastname: Samassekou
authors.forename: Abba
authors.initials: A
authors.lastname: Malina
authors.forename: Josée
authors.initials: J
authors.lastname: Hébert
authors.forename: Ju
authors.initials: J
authors.lastname: Yan
mesh_terms: D002869:Chromosome Aberrations; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics*; D016615:Telomere / Q000235:genetics*; D059505:Telomere Homeostasis / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; C509186:TERT protein, human; D019098:Telomerase
references.citation: Leukemia. 1997 Feb;11(2):190-4
references.pmid: 9009079
references.citation: Genes Dev. 2013 Jan 1;27(1):18-23
references.pmid: 23307865
references.citation: Cancer Res. 2007 Aug 1;67(15):7072-7
references.pmid: 17652140
references.citation: Cancer Res. 1999 Sep 1;59(17):4175-9
references.pmid: 10485449
references.citation: Biochem Biophys Res Commun. 1998 Jun 29;247(3):765-72
references.pmid: 9647768
references.citation: Nat Biotechnol. 2009 Dec;27(12):1181-5
references.pmid: 19935656
references.citation: J Biochem. 2011 Jan;149(1):5-14
references.pmid: 20937668
references.citation: Mech Ageing Dev. 2008 Jan-Feb;129(1-2):99-108
references.pmid: 18215414
references.citation: Nat Med. 1997 Nov;3(11):1271-4
references.pmid: 9359704
references.citation: Science. 1995 Dec 8;270(5242):1601-7
references.pmid: 7502069
references.citation: Oncogene. 2002 Jan 21;21(4):680-7
references.pmid: 11850796
references.citation: Nucleic Acids Res. 2013 Jan;41(2):e34
references.pmid: 22923525
references.citation: Mol Cell Biol. 2004 Nov;24(22):9948-57
references.pmid: 15509797
references.citation: Clin Cancer Res. 2008 Jul 1;14(13):4134-40
references.pmid: 18593991
references.citation: Cancer Res. 2006 Sep 1;66(17):8918-24
references.pmid: 16951210
references.citation: PLoS Genet. 2009 Jan;5(1):e1000357
references.pmid: 19180191
references.citation: EMBO J. 2009 Apr 8;28(7):799-809
references.pmid: 19214183
references.citation: Nature. 1982 Dec 23;300(5894):765-7
references.pmid: 6960256
references.citation: Leuk Lymphoma. 2004 Sep;45(9):1775-81
references.pmid: 15223635
references.citation: Neoplasia. 2011 Jun;13(6):550-60
references.pmid: 21677878
references.citation: Oncogene. 2005 Nov 24;24(53):7893-901
references.pmid: 16116482
references.citation: Cell. 2004 Oct 29;119(3):355-68
references.pmid: 15507207
references.citation: Mol Cell Biol. 2001 Mar;21(5):1819-27
references.pmid: 11238918
references.citation: Neoplasia. 2009 Nov;11(11):1146-54
references.pmid: 19881950