Telomere Biology of Human Hematopoietic Stem Cells

Weissman I.L. Stem cells: units of development, units of regeneration, and units in evolution. Cell. 2000; 100: 157–168.

Smith C. Hematopoietic stem cells and hematopoiesis. Cancer Control. 2003; 10: 9–16.

Fruehauf S. , Seggewiss R. It's moving day: factors affecting peripheral blood stem mobilization and strategies for improvement. Br J Haematol. 2003; 122: 360–375.

Lansdorp P.M. Self-renewal of stem cells. Biol Blood Marrow Transplant. 1997; 3: 171–178.

Reya T. , Morrison S.J. , Clarke M.F. Stem cells, cancer, and cancer stem cells. Nature. 2001; 414: 105–111.

Lansdorp P.M. Telomere length and proliferation potential of hematopoietic stem cells. J Cell Sci. 1995; 108(pt 1): 1–6.

Morrison S.J. , Prowse K.R. , Ho P. Telomerase activity in hematopoietic cells is associated with self-renewal potential. Immunity. 1996; 5: 207–216.

Collins K. , Mitchell J.R. Telomerase in the human organism. Oncogene. 2002; 21: 564–579.

Moyzis R.K. , Buckingham J.M. , Cram L.S. A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci U S A. 1988; 85: 6622–6626.

de Lange T. , Shiue L. , Myers R.M. Structure and variability of human chromosome ends. Mol Cell Biol. 1990; 10: 518–527.

de Lange T. Human telomeres are attached to the nuclear matrix. EMBO J. 1992; 11: 717–724.

Giraldo R. , Rhodes D. The yeast telomere-binding protein RAP1 binds to and promotes the formation of DNA quadruplexes in telomeric DNA. EMBO J. 1994; 13: 2411–2420.

Chikashige Y. , Ding D.Q. , Funabiki H. Telomere-led premeiotic chromosome movement in fission yeast. Science. 1994; 264: 270–273.

Henderson E.R. , Blackburn E.H. An overhanging 3′ terminus is a conserved feature of telomeres. Mol Cell Biol. 1989; 9: 345–348.

McElligott R. , Wellinger R.J. The terminal DNA structure of mammalian chromosomes. EMBO J. 1997; 16: 3705–3714.

Wright W.E. , Tesmer V.M. , Huffman K.E. Normal human chromosomes have long G-rich telomeric overhangs at one end. Genes Dev. 1997; 11: 2801–2809.

Griffith J.D. , Comeau L. , Rosenfield S. Mammalian telomeres end in a large duplex loop. Cell. 1999; 97: 503–514.

Chong L. , van Steensel B. , Broccoli D. A human telomeric protein. Science. 1995; 270: 1663–1667.

Broccoli D. , Smogorzewska A. , Chong L. Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2. Nat Genet. 1997; 17: 231–235.

Bilaud T. , Brun C. , Ancelin K. Telomeric localization of TRF2, a novel human telobox protein. Nat Genet. 1997; 17: 236–239.

Baumann P. , Cech T.R. Pot1, the putative telomere end-binding protein in fission yeast and humans. Science. 2001; 292: 1171–1175.

Colgin L.M. , Baran K. , Baumann P. Human POT1 facilitates telomere elongation by telomerase. Curr Biol. 2003; 13: 942–946.

Smith S. , Giriat I. , Schmitt A. Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. Science. 1998; 282: 1484–1487.

Smith S. , de Lange T. Tankyrase promotes telomere elongation in human cells. Curr Biol. 2000; 10: 1299–1302.

Li B. , Oestreich S. , de Lange T. Identification of human Rap1: implications for telomere evolution. Cell. 2000; 101: 471–483.

Bianchi A. , de Lange T. Ku binds telomeric DNA in vitro. J Biol Chem. 1999; 274: 21223–21227.

Chai W. , Ford L.P. , Lenertz L. Human Ku70/80 associates physically with telomerase through interaction with hTERT. J Biol Chem. 2002; 277: 47242–47247.

van Steensel B. , de Lange T. Control of telomere length by the human telomeric protein TRF1. Nature. 1997; 385: 740–743.

van Steensel B. , Smogorzewska A. , de Lange T. TRF2 protects human telomeres from end-to-end fusions. Cell. 1998; 92: 401–413.

Karlseder J. , Broccoli D. , Dai Y. p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science. 1999; 283: 1321–1325.

Harley C.B. , Futcher A.B. , Greider C.W. Telomeres shorten during ageing of human fibroblasts. Nature. 1990; 345: 458–460.

Hayflick L. , Moorhead P.S. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961; 25: 585–621.

Harley C.B. Telomere loss: mitotic clock or genetic time bomb? Mutat Res. 1991; 256: 271–282.

Harley C.B. , Vaziri H. , Counter C.M. The telomere hypothesis of cellular aging. Exp Gerontol. 1992; 27: 375–382.

Bodnar A.G. , Ouellette M. , Frolkis M. Extension of life-span by introduction of telomerase into normal human cells. Science. 1998; 279: 349–352.

Vaziri H. , Benchimol S. Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span. Curr Biol. 1998; 8: 279–282.

Mathon N.F. , Lloyd A.C. Cell senescence and cancer. Nat Rev Cancer. 2001; 1: 203–213.

Martens U.M. , Zijlmans J.M. , Poon S.S. Short telomeres on human chromosome 17p. Nat Genet. 1998; 18: 76–80.

Hemann M.T. , Strong M.A. , Hao L.Y. The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell. 2001; 107: 67–77.

Lansdorp P.M. Repair of telomeric DNA prior to replicative senescence. Mech Ageing Dev. 2000; 118: 23–34.

Huffman K.E. , Levene S.D. , Tesmer V.M. Telomere shortening is proportional to the size of the G-rich telomeric 3′ overhang. J Biol Chem. 2000; 275: 19719–19722.

Blackburn E.H. Telomere states and cell fates. Nature. 2000; 408: 53–56.

Karlseder J. , Smogorzewska A. , de Lange T. Senescence induced by altered telomere state, not telomere loss. Science. 2002; 295: 2446–2449.

Masutomi K. , Yu E.Y. , Khurts S. Telomerase maintains telomere structure in normal human cells. Cell. 2003; 114: 241–253.

Harley C.B. , Kim N.W. , Prowse K.R. Telomerase, cell immortality, and cancer. Cold Spring Harb Symp Quant Biol. 1994; 59: 307–315.

Liu J.P. Studies of the molecular mechanisms in the regulation of telomerase activity. FASEB J. 1999; 13: 2091–2104.

Verfaillie C.M. , Pera M.F. , Lansdorp P.M. Stem cells: hype and reality. Hematology (Am Soc Hematol Educ Program). 2002: 369–391.

Vojta P.J. , Barrett J.C. Genetic analysis of cellular senescence. Biochim Biophys Acta. 1995; 1242: 29–41.

Sandell L.L. , Zakian V.A. Loss of a yeast telomere: arrest, recovery, and chromosome loss. Cell. 1993; 75: 729–739.

Blackburn E.H. Switching and signaling at the telomere. Cell. 2001; 106: 661–673.

Abraham R.T. Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev. 2001; 15: 2177–2196.

Chin L. , Artandi S.E. , Shen Q. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell. 1999; 97: 527–538.

Metz T. , Harris A.W. , Adams J.M. Absence of p53 allows direct immortalization of hematopoietic cells by the myc and raf oncogenes. Cell. 1995; 82: 29–36.

Greider C.W. , Blackburn E.H. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell. 1985; 43: 405–413.

Morin G.B. The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell. 1989; 59: 521–529.

Feng J. , Funk W.D. , Wang S.S. The RNA component of human telomerase. Science. 1995; 269: 1236–1241.

Autexier C. , Pruzan R. , Funk W.D. Reconstitution of human telomerase activity and identification of a minimal functional region of the human telomerase RNA. EMBO J. 1996; 15: 5928–5935.

Kondo S. , Tanaka Y. , Kondo Y. Antisense telomerase treatment: induction of two distinct pathways, apoptosis and differentiation. FASEB J. 1998; 12: 801–811.

Niida H. , Matsumoto T. , Satoh H. Severe growth defect in mouse cells lacking the telomerase RNA component. Nat Genet. 1998; 19: 203–206.

Lee H.W. , Blasco M.A. , Gottlieb G.J. Essential role of mouse telomerase in highly proliferative organs. Nature. 1998; 392: 569–574.

Vulliamy T. , Marrone A. , Goldman F. The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature. 2001; 413: 432–435.

Mason P.J. Stem cells, telomerase and dyskeratosis congenita. Bioessays. 2003; 25: 126–133.

Vulliamy T. , Marrone A. , Dokal I. Association between aplastic anaemia and mutations in telomerase RNA. Lancet. 2002; 359: 2168–2170.

Nakamura T.M. , Morin G.B. , Chapman K.B. Telomerase catalytic subunit homologs from fission yeast and human. Science. 1997; 277: 955–959.

Meyerson M. , Counter C.M. , Eaton E.N. hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization. Cell. 1997; 90: 785–795.

Counter C.M. , Meyerson M. , Eaton E.N. Telomerase activity is restored in human cells by ectopic expression of hTERT (hEST2), the catalytic subunit of telomerase. Oncogene. 1998; 16: 1217–1222.

Yang J. , Chang E. , Cherry A.M. Human endothelial cell life extension by telomerase expression. J Biol Chem. 1999; 274: 26141–26148.

Jiang X.R. , Jimenez G. , Chang E. Telomerase expression in human somatic cells does not induce changes associated with a transformed phenotype. Nat Genet. 1999; 21: 111–114.

MacKenzie K.L. , Franco S. , May C. Mass cultured human fibroblasts overexpressing hTERT encounter a growth crisis following an extended period of proliferation. Exp Cell Res. 2000; 259: 336–350.

Dickson M.A. , Hahn W.C. , Ino Y. Human keratinocytes that express hTERT and also bypass a p16(INK4a)-enforced mechanism that limits life span become immortal yet retain normal growth and differentiation characteristics. Mol Cell Biol. 2000; 20: 1436–1447.

Kolquist K.A. , Ellisen L.W. , Counter C.M. Expression of TERT in early premalignant lesions and a subset of cells in normal tissues. Nat Genet. 1998; 19: 182–186.

Harley C.B. , Kim N.W. Telomerase and cancer. Important Adv Oncol. 1996: 57–67.

Reddel R.R. Genes involved in the control of cellular proliferative potential. Ann NY Acad Sci. 1998; 854: 8–19.

Hahn W.C. , Meyerson M. Telomerase activation, cellular immortalization and cancer. Ann Med. 2001; 33: 123–129.

Stewart S.A. , Weinberg R.A. Senescence: does it all happen at the ends? Oncogene. 2002; 21: 627–630.

Vaziri H. , Dragowska W. , Allsopp R.C. Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. Proc Natl Acad Sci U S A. 1994; 91: 9857–9860.

Lansdorp P.M. , Dragowska W. , Thomas T.E. Age-related decline in proliferative potential of purified stem cell candidates. Blood Cells. 1994; 20: 376–381.

Ohyashiki J.H. , Sashida G. , Tauchi T. Telomeres and telomerase in hematologic neoplasia. Oncogene. 2002; 21: 680–687.

Lansdorp P.M. , Poon S. , Chavez E. Telomeres in the haemopoietic system. Ciba Found Symp. 1997; 211: 209–222.

Rufer N. , Brummendorf T.H. , Kolvraa S. Telomere fluorescence measurements in granulocytes and T lymphocyte subsets point to a high turnover of hematopoietic stem cells and memory T cells in early childhood. J Exp Med. 1999; 190: 157–167.

Frenck R.W. Jr , Blackburn E.H. , Shannon K.M. The rate of telomere sequence loss in human leukocytes varies with age. Proc Natl Acad Sci U S A. 1998; 95: 5607–5610.

Rufer N. , Dragowska W. , Thornbury G. Telomere length dynamics in human lymphocyte subpopulations measured by flow cytometry. Nat Biotechnol. 1998; 16: 743–747.

Slagboom P.E. , Droog S. , Boomsma D.I. Genetic determination of telomere size in humans: a twin study of three age groups. Am J Hum Genet. 1994; 55: 876–882.

Lansdorp P.M. , Verwoerd N.P. , van de Rijke F.M. Heterogeneity in telomere length of human chromosomes. Hum Mol Genet. 1996; 5: 685–691.

Baerlocher G.M. , Roth A. , Lansdorp P.M. Telomeres in hematopoietic stem cells. Ann NY Acad Sci. 2003; 996: 44–48.

Ball S.E. , Gibson F.M. , Rizzo S. Progressive telomere shortening in aplastic anemia. Blood. 1998; 91: 3582–3592.

Brummendorf T.H. , Rufer N. , Holyoake T.L. Telomere length dynamics in normal individuals and in patients with hematopoietic stem cell-associated disorders. Ann N Y Acad Sci. 2001; 938: 293–304.

Brummendorf T.H. , Maciejewski J.P. , Mak J. Telomere length in leukocyte subpopulations of patients with aplastic anemia. Blood. 2001; 97: 895–900.

Leteurtre F. , Li X. , Guardiola P. Accelerated telomere shortening and telomerase activation in Fanconi's anaemia. Br J Haematol. 1999; 105: 883–893.

Vulliamy T.J. , Knight S.W. , Mason P.J. Very short telomeres in the peripheral blood of patients with X-linked and autosomal dyskeratosis congenita. Blood Cells Mol Dis. 2001; 27: 353–357.

Lee J.J. , Kook H. , Chung I.J. Telomere length changes in patients with aplastic anaemia. Br J Haematol. 2001; 112: 1025–1030.

Counter C.M. , Gupta J. , Harley C.B. Telomerase activity in normal leukocytes and in hematologic malignancies. Blood. 1995; 85: 2315–2320.

Ohyashiki J.H. , Iwama H. , Yahata N. Telomere stability is frequently impaired in high-risk groups of patients with myelodysplastic syndromes. Clin Cancer Res. 1999; 5: 1155–1160.

Engelhardt M. , Mackenzie K. , Drullinsky P. Telomerase activity and telomere length in acute and chronic leukemia, pre- and postex vivo culture. Cancer Res. 2000; 60: 610–617.

Ohyashiki K. , Iwama H. , Yahata N. Telomere dynamics in myelodysplastic syndromes and acute leukemic transformation. Leuk Lymphoma. 2001; 42: 291–299.

Terasaki Y. , Okumura H. , Ohtake S. Accelerated telomere length shortening in granulocytes: a diagnostic marker for myeloproliferative diseases. Exp Hematol. 2002; 30: 1399–1404.

Ohyashiki K. , Ohyashiki J.H. , Iwama H. Telomerase activity and cytogenetic changes in chronic myeloid leukemia with disease progression. Leukemia. 1997; 11: 190–194.

Iwama H. , Ohyashiki K. , Ohyashiki J.H. The relationship between telomere length and therapy-associated cytogenetic responses in patients with chronic myeloid leukemia. Cancer. 1997; 79: 1552–1560.

Hayashi S. , Iwama H. , Yahata N. Malignancy: subsequential alterations of telomeric DNA length correlate with cytogenetic response in chronic myeloid leukemia treated with interferon alpha. Hematology. 1999; 4: 1–10.

Ohyashiki K. , Iwama H. , Tauchi T. Telomere dynamics and genetic instability in disease progression of chronic myeloid leukemia. Leuk Lymphoma. 2000; 40: 49–56.

Brummendorf T.H. , Holyoake T.L. , Rufer N. Prognostic implications of differences in telomere length between normal and malignant cells from patients with chronic myeloid leukemia measured by flow cytometry. Blood. 2000; 95: 1883–1890.

Brummendorf T.H. , Ersoz I. , Hartmann U. Normalization of previously shortened telomere length under treatment with imatinib argues against a preexisting telomere length deficit in normal hematopoietic stem cells from patients with chronic myeloid leukemia. Ann N Y Acad Sci. 2003; 996: 26–38.

Theimer C.A. , Finger L.D. , Trantirek L. Mutations linked to dyskeratosis congenita cause changes in the structural equilibrium in telomerase RNA. Proc Natl Acad Sci U S A. 2003; 100: 449–454.

Greenberg P. , Cox C. , LeBeau M.M. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997; 89: 2079–2088.

Engelhardt M. , Ozkaynak M.F. , Drullinsky P. Telomerase activity and telomere length in pediatric patients with malignancies undergoing chemotherapy. Leukemia. 1998; 12: 13–24.

Franco S. , Ozkaynak M.F. , Sandoval C. Telomere dynamics in childhood leukemia and solid tumors: a follow-up study. Leukemia. 2003; 17: 401–410.

Notaro R. , Cimmino A. , Tabarini D. In vivo telomere dynamics of human hematopoietic stem cells. Proc Natl Acad Sci U S A. 1997; 94: 13782–13785.

Akiyama M. , Hoshi Y. , Sakurai S. Changes of telomere length in children after hematopoietic stem cell transplantation. Bone Marrow Transplant. 1998; 21: 167–171.

Wynn R.F. , Cross M.A. , Hatton C. Accelerated telomere shortening in young recipients of allogeneic bone-marrow transplants. Lancet. 1998; 351: 178–181.

Shay J.W. Accelerated telomere shortening in bone-marrow recipients. Lancet. 1998; 351: 153–154.

Lee J. , Kook H. , Chung I. Telomere length changes in patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant. 1999; 24: 411–415.

Brummendorf T.H. , Rufer N. , Baerlocher G.M. Limited telomere shortening in hematopoietic stem cells after transplantation. Ann N Y Acad Sci. 2001; 938: 1–8.

Rufer N. , Brummendorf T.H. , Chapuis B. Accelerated telomere shortening in hematological lineages is limited to the first year following stem cell transplantation. Blood. 2001; 97: 575–577.

Thornley I. , Sutherland R. , Wynn R. Early hematopoietic reconstitution after clinical stem cell transplantation: evidence for stochastic stem cell behavior and limited acceleration in telomere loss. Blood. 2002; 99: 2387–2396.

de Pauw E.S. , Otto S.A. , Wijnen J.T. Long-term follow-up of recipients of allogeneic bone marrow grafts reveals no progressive telomere shortening and provides no evidence for haematopoietic stem cell exhaustion. Br J Haematol. 2002; 116: 491–496.

Mathioudakis G. , Storb R. , McSweeney P.A. Polyclonal hematopoiesis with variable telomere shortening in human long-term allogeneic marrow graft recipients. Blood. 2000; 96: 3991–3994.

Akiyama M. , Asai O. , Kuraishi Y. Shortening of telomeres in recipients of both autologous and allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2000; 25: 441–447.

Awaya N. , Baerlocher G.M. , Manley T.J. Telomere shortening in hematopoietic stem cell transplantation: a potential mechanism for late graft failure? Biol Blood Marrow Transplant. 2002; 8: 597–600.

Broccoli D. , Young J.W. , de Lange T. Telomerase activity in normal and malignant hematopoietic cells. Proc Natl Acad Sci U S A. 1995; 92: 9082–9086.

Hiyama K. , Hirai Y. , Kyoizumi S. Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J Immunol. 1995; 155: 3711–3715.

Chiu C.P. , Dragowska W. , Kim N.W. Differential expression of telomerase activity in hematopoietic progenitors from adult human bone marrow. Stem Cells. 1996; 14: 239–248.

Zhang W. , Piatyszek M.A. , Kobayashi T. Telomerase activity in human acute myelogenous leukemia: inhibition of telomerase activity by differentiation-inducing agents. Clin Cancer Res. 1996; 2: 799–803.

Weng N.P. , Levine B.L. , June C.H. Regulated expression of telomerase activity in human T lymphocyte development and activation. J Exp Med. 1996; 183: 2471–2479.

Engelhardt M. , Kumar R. , Albanell J. Telomerase regulation, cell cycle, and telomere stability in primitive hematopoietic cells. Blood. 1997; 90: 182–193.

Ohyashiki K. , Ohyashiki J.H. Measurement of telomerase activity in human hematopoietic cells and neoplastic disorders. Methods Mol Med. 2002; 68: 279–299.

Weng N.P. , Hodes R.J. The role of telomerase expression and telomere length maintenance in human and mouse. J Clin Immunol. 2000; 20: 257–267.

Weng N. Interplay between telomere length and telomerase in human leukocyte differentiation and aging. J Leukoc Biol. 2001; 70: 861–867.

Yui J. , Chiu C.P. , Lansdorp P.M. Telomerase activity in candidate stem cells from fetal liver and adult bone marrow. Blood. 1998; 91: 3255–3262.

Uchida N. , Otsuka T. , Shigematsu H. Differential gene expression of human telomerase-associated protein hTERT and TEP1 in human hematopoietic cells. Leuk Res. 1999; 23: 1127–1132.

Kim N.W. , Piatyszek M.A. , Prowse K.R. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994; 266: 2011–2015.

Sharma H.W. , Sokoloski J.A. , Perez J.R. Differentiation of immortal cells inhibits telomerase activity. Proc Natl Acad Sci U S A. 1995; 92: 12343–12346.

Bestilny L.J. , Brown C.B. , Miura Y. Selective inhibition of telomerase activity during terminal differentiation of immortal cell lines. Cancer Res. 1996; 56: 3796–3802.

Savoysky E. , Yoshida K. , Ohtomo T. Down-regulation of telomerase activity is an early event in the differentiation of HL60 cells. Biochem Biophys Res Commun. 1996; 226: 329–334.

Xu D. , Gruber A. , Peterson C. Suppression of telomerase activity in HL60 cells after treatment with differentiating agents. Leukemia. 1996; 10: 1354–1357.

Albanell J. , Han W. , Mellado B. Telomerase activity is repressed during differentiation of maturation-sensitive but not resistant human tumor cell lines. Cancer Res. 1996; 56: 1503–1508.

Yamada O. , Takanashi M. , Ujihara M. Down-regulation of telomerase activity is an early event of cellular differentiation without apparent telomeric DNA change. Leuk Res. 1998; 22: 711–717.

Sharma S. , Raymond E. , Soda H. Dimethyl sulfoxide (DMSO) causes a reversible inhibition of telomerase activity in a Burkitt lymphoma cell line. Leuk Res. 1998; 22: 663–670.

Pendino F. , Flexor M. , Delhommeau F. Retinoids down-regulate telomerase and telomere length in a pathway distinct from leukemia cell differentiation. Proc Natl Acad Sci U S A. 2001; 98: 6662–6667.

Zhu X. , Kumar R. , Mandal M. Cell cycle-dependent modulation of telomerase activity in tumor cells. Proc Natl Acad Sci U S A. 1996; 93: 6091–6095.

Holt S.E. , Wright W.E. , Shay J.W. Regulation of telomerase activity in immortal cell lines. Mol Cell Biol. 1996; 16: 2932–2939.

Weng N.P. , Hathcock K.S. , Hodes R.J. Regulation of telomere length and telomerase in T and B cells: a mechanism for maintaining replicative potential. Immunity. 1998; 9: 151–157.

Elwood N.J. , Jiang X.R. , Chiu C.P. Enhanced long-term survival, but no increase in replicative capacity, following retroviral transduction of human cord blood CD34+ cells with human telomerase reverse transcriptase. Haematologica. 2004; 89: 375–376.

Roth A. , Yssel H. , Pene J. Telomerase levels control the lifespan of human T lymphocytes. Blood. 2003; 102: 849–857.

Cao Y. , Li H. , Deb S. TERT regulates cell survival independent of telomerase enzymatic activity. Oncogene. 2002; 21: 3130–3138.

Yamada O. , Oshimi K. , Motoji T. Telomeric DNA in normal and leukemic blood cells. J Clin Invest. 1995; 95: 1117–1123.

Ohyashiki J.H. , Ohyashiki K. , Iwama H. Clinical implications of telomerase activity levels in acute leukemia. Clin Cancer Res. 1997; 3: 619–625.

Bryan T.M. , Englezou A. , Dalla-Pozza L. Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nat Med. 1997; 3: 1271–1274.

Henson J.D. , Neumann A.A. , Yeager T.R. Alternative lengthening of telomeres in mammalian cells. Oncogene. 2002; 21: 598–610.

Yeager T.R. , Neumann A.A. , Englezou A. Telomerase-negative immortalized human cells contain a novel type of promyelocytic leukemia (PML) body. Cancer Res. 1999; 59: 4175–4179.

Elwood N.J. , Smith C.A. Current status of retroviral vector mediated gene transfer into human hematopoietic stem cells. Leuk Lymphoma. 2001; 41: 465–482.

Bearss D.J. , Hurley L.H. , Von Hoff D.D. Telomere maintenance mechanisms as a target for drug development. Oncogene. 2000; 19: 6632–6641.

Wang E.S. , Wu K. , Chin A.C. Telomerase inhibition with an oligonucleotide telomerase template antagonist: in vitro and in vivo studies in multiple myeloma and lymphoma. Blood. 2004; 103: 258–266.