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PMID: 16172394 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Dissociation of telomerase activity and telomere length maintenance in primitive human hematopoietic cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 40 ·2005-10-04 ·Pages 14398-403

Wang JC, Warner JK, Erdmann N, Lansdorp PM, Harrington L, Dick JE

Abstract

Primitive human hematopoietic cells have low endogenous telomerase activity, yet telomeres are not maintained. In contrast, ectopic telomerase expression in fibroblasts and other cells leads to telomere length maintenance or elongation. It is unclear whether this disparity can be attributed to telomerase level or stems from fundamentally different telomere biology. Here, we show that telomerase overexpression does not prevent proliferation-associated telomere shortening in human hematopoietic cells, pointing to the existence of cell type-specific differences in telomere dynamics. Furthermore, we observed eventual stabilization of telomere length without detectable changes in telomerase activity during establishment of two leukemic cell lines from normal cord blood cells, indicating that additional cooperating events are required for telomere maintenance in immortalized human hematopoietic cells.

MeSH Terms
Cell Proliferation Cloning, Molecular DNA, Complementary/genetics DNA-Binding Proteins/metabolism Fetal Blood/cytology Flow Cytometry Fluorescein-5-isothiocyanate HeLa Cells Hematopoietic Stem Cells/enzymology Humans Lentivirus Leukemia/enzymology Telomerase/metabolism Telomere/genetics
Chemicals
DNA, Complementary DNA-Binding Proteins Telomerase Fluorescein-5-isothiocyanate
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wang J C Y
Department of Molecular and Medical Genetics, University of Toronto, Toronto, ON, Canada M5S 1A8.
Warner J K
Erdmann N
Lansdorp P M
Harrington L
Dick J E
References (47)
47 references, click to expand
  1. Telomere structure and telomerase expression during mouse development and tumorigenesis.
    Eur J Cancer. 1997 Apr;33(5):792-800 PMID: 9282119
  2. Transduction of human CD34+ CD38- bone marrow and cord blood-derived SCID-repopulating cells with third-generation lentiviral vectors.
    Mol Ther. 2000 Jun;1(6):566-73 PMID: 10933981
  3. Telomerase regulation, cell cycle, and telomere stability in primitive hematopoietic cells.
    Blood. 1997 Jul 1;90(1):182-93 PMID: 9207452
  4. Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age.
    Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9857-60 PMID: 7937905
  5. Functional conservation of the telomerase protein Est1p in humans.
    Curr Biol. 2003 Apr 15;13(8):698-704 PMID: 12699629
  6. Human endothelial cell life extension by telomerase expression.
    J Biol Chem. 1999 Sep 10;274(37):26141-8 PMID: 10473565
  7. Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript.
    Blood. 1997 Aug 1;90(3):1192-9 PMID: 9242552
  8. Telomerase activity in normal and malignant hematopoietic cells.
    Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9082-6 PMID: 7568077
  9. Est1 and Cdc13 as comediators of telomerase access.
    Science. 1999 Oct 1;286(5437):117-20 PMID: 10506558
  10. Developmental and tissue-specific regulation of mouse telomerase and telomere length.
    Proc Natl Acad Sci U S A. 1995 May 23;92(11):4818-22 PMID: 7761406
  11. Telomere dynamics in cancer progression and prevention: fundamental differences in human and mouse telomere biology.
    Nat Med. 2000 Aug;6(8):849-51 PMID: 10932210
  12. The hallmarks of cancer.
    Cell. 2000 Jan 7;100(1):57-70 PMID: 10647931
  13. Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization.
    Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14723-8 PMID: 9843956
  14. Telomerase activity in candidate stem cells from fetal liver and adult bone marrow.
    Blood. 1998 May 1;91(9):3255-62 PMID: 9558381
  15. Telomere length dynamics in human lymphocyte subpopulations measured by flow cytometry.
    Nat Biotechnol. 1998 Aug;16(8):743-7 PMID: 9702772
  16. Telomere loss, senescence, and genetic instability in CD4+ T lymphocytes overexpressing hTERT.
    Blood. 2005 Jul 1;106(1):43-50 PMID: 15741219
  17. Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span.
    Curr Biol. 1998 Feb 26;8(5):279-82 PMID: 9501072
  18. Telomeric DNA in normal and leukemic blood cells.
    J Clin Invest. 1995 Mar;95(3):1117-23 PMID: 7883960
  19. The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability.
    Cell. 2001 Oct 5;107(1):67-77 PMID: 11595186
  20. Telomere reduction of specific chromosome translocation in acute myelocytic leukemia.
    Jpn J Cancer Res. 1994 Feb;85(2):127-30 PMID: 7908283
  21. Human telomerase contains evolutionarily conserved catalytic and structural subunits.
    Genes Dev. 1997 Dec 1;11(23):3109-15 PMID: 9389643
  22. Positive and negative regulation of telomerase access to the telomere.
    J Cell Sci. 2000 Oct;113 Pt 19:3357-64 PMID: 10984427
  23. Reconstituting telomerase activity using the telomerase catalytic subunit prevents the telomere shorting and replicative senescence in human osteoblasts.
    J Bone Miner Res. 2001 Aug;16(8):1453-64 PMID: 11499868
  24. Effect of TERT over-expression on the long-term transplantation capacity of hematopoietic stem cells.
    Nat Med. 2003 Apr;9(4):369-71 PMID: 12669037
  25. Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia.
    N Engl J Med. 2005 Apr 7;352(14):1413-24 PMID: 15814878
  26. Pot1, the putative telomere end-binding protein in fission yeast and humans.
    Science. 2001 May 11;292(5519):1171-5 PMID: 11349150
  27. Effects of telomerase modulation in human hematopoietic progenitor cells.
    Stem Cells. 2004;22(5):741-9 PMID: 15342938
  28. Telomere length measurement by fluorescence in situ hybridization and flow cytometry: tips and pitfalls.
    Cytometry. 2002 Feb 1;47(2):89-99 PMID: 11813198
  29. Direct evidence for cooperating genetic events in the leukemic transformation of normal human hematopoietic cells.
    Leukemia. 2005 Oct;19(10 ):1794-805 PMID: 16094415
  30. Distinct classes of human stem cells that differ in proliferative and self-renewal potential.
    Nat Immunol. 2001 Jan;2(1):75-82 PMID: 11135582
  31. Acute non-lymphoblastic leukaemia with t(16;21): case report with a review of the literature.
    Clin Lab Haematol. 1995 Sep;17(3):243-6 PMID: 8719898
  32. Distinct dosage requirements for the maintenance of long and short telomeres in mTert heterozygous mice.
    Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):6080-5 PMID: 15079066
  33. The RNA component of human telomerase.
    Science. 1995 Sep 1;269(5228):1236-41 PMID: 7544491
  34. Differential expression of telomerase activity in hematopoietic progenitors from adult human bone marrow.
    Stem Cells. 1996 Mar;14(2):239-48 PMID: 8991544
  35. Telomerase activity in normal leukocytes and in hematologic malignancies.
    Blood. 1995 May 1;85(9):2315-20 PMID: 7727765
  36. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell.
    Nat Med. 1997 Jul;3(7):730-7 PMID: 9212098
  37. Telomerase regulation: not just flipping the switch.
    Curr Opin Genet Dev. 2002 Feb;12(1):80-5 PMID: 11790559
  38. Extension of life-span by introduction of telomerase into normal human cells.
    Science. 1998 Jan 16;279(5349):349-52 PMID: 9454332
  39. Switching and signaling at the telomere.
    Cell. 2001 Sep 21;106(6):661-73 PMID: 11572773
  40. Transfer of the human telomerase reverse transcriptase (TERT) gene into T lymphocytes results in extension of replicative potential.
    Blood. 2001 Aug 1;98(3):597-603 PMID: 11468156
  41. Clinical implications of telomerase activity levels in acute leukemia.
    Clin Cancer Res. 1997 Apr;3(4):619-25 PMID: 9815729
  42. Telomere length measurements in leukocyte subsets by automated multicolor flow-FISH.
    Cytometry A. 2003 Sep;55(1):1-6 PMID: 12938182
  43. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity.
    Nat Immunol. 2004 Jul;5(7):738-43 PMID: 15170211
  44. The establishment of telomerase-immortalized cell lines representing human chromosome instability syndromes.
    Hum Mol Genet. 2000 Feb 12;9(3):403-11 PMID: 10655550
  45. Gene transfer by lentiviral vectors is limited by nuclear translocation and rescued by HIV-1 pol sequences.
    Nat Genet. 2000 Jun;25(2):217-22 PMID: 10835641
  46. Retroviral transduction of TLS-ERG initiates a leukemogenic program in normal human hematopoietic cells.
    Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8239-44 PMID: 9653171
  47. The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita.
    Nature. 2001 Sep 27;413(6854):432-5 PMID: 11574891
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0504161102
Published
2005-10-04
Epub
2005-00-19
Pages
14398-403
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1242297
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0504161102 PMC Full Text View journal details
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