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Cancer Stem Cells: Potential Targets for Molecular Medicine

  • Isabel G. Newton
  • Catriona H. M. Jamieson
Chapter
Part of the Molecular Pathology Library book series (MPLB, volume 4)

Abstract

The concept of stem cells has become so pervasive in our society that most people have some idea of what stem cells are and some opinion regarding the debates surrounding their use in science and medicine. Stem cells, best studied in the hematopoietic system, are defined by their singular capacity to renew themselves and give rise to more specialized cells that comprise the organs and tissues of the body. Nevertheless, the idea that cancers, too, derive from stem cells or their progenitors is not as widely recognized. Even less well understood are the diagnostic and therapeutic implications of such a hypothesis.

Keywords

Acute Myeloid Leukemia Chronic Myelogenous Leukemia Cancer Stem Cell Blast Crisis Leukemia Stem Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Spangrude GJ, Heimfeld S, Weissman IL. Purification and characterization of mouse hematopoietic stem cells. Science. 1988;241(4861):58–62.CrossRefPubMedGoogle Scholar
  2. 2.
    Baum CM, Weissman IL, Tsukamoto AS, Buckle AM, Peault B. Isolation of a candidate human hematopoietic stem-cell population. Proc Natl Acad Sci USA. 1992;89(7):2804–2808.CrossRefPubMedGoogle Scholar
  3. 3.
    Osawa M, Hanada K, Hamada H, Nakauchi H. Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science. 1996;273(5272):242–245.CrossRefPubMedGoogle Scholar
  4. 4.
    Till JE, Mc CE. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961;14:213–222.CrossRefPubMedGoogle Scholar
  5. 5.
    Park CH, Bergsagel DE, McCulloch EA. Mouse myeloma tumor stem cells: a primary cell culture assay. J Natl Cancer Inst. 1971;46(2):411–422.PubMedGoogle Scholar
  6. 6.
    Bruce W, VanderGaag H. A quantitative assay for the number of murine lymphoma cells capable of proliferation in vivo. Nature. 1963;199:2.CrossRefGoogle Scholar
  7. 7.
    Wodinsky I, Swiniarski J, Kensler CJ. Spleen colony studies of leukemia L1210. 3. Differential sensitivities of normal hematopoietic and resistant L1210 colony-forming cells to 6-mercaptopurine (NSC-755). Cancer Chemother Rep. 1968;52(2):251–255.PubMedGoogle Scholar
  8. 8.
    Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367(6464):645–648.CrossRefPubMedGoogle Scholar
  9. 9.
    Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3(7):730–737.CrossRefPubMedGoogle Scholar
  10. 10.
    Blair A, Hogge DE, Ailles LE, Lansdorp PM, Sutherland HJ. Lack of expression of Thy-1 (CD90) on acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo. Blood. 1997;89(9):3104–3112.PubMedGoogle Scholar
  11. 11.
    Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105–111.CrossRefPubMedGoogle Scholar
  12. 12.
    Jamieson CH, Ailles LE, Dylla SJ, et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med. 2004;351(7):657–667.CrossRefPubMedGoogle Scholar
  13. 13.
    Clarke MF, Dick JE, Dirks PB, et al. Cancer stem cells – perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res. 2006;66(19):9339–9344.CrossRefPubMedGoogle Scholar
  14. 14.
    Diehn M, Clarke MF. Cancer stem cells and radiotherapy: new insights into tumor radioresistance. J Natl Cancer Inst. 2006;98(24):1755–1757.CrossRefPubMedGoogle Scholar
  15. 15.
    Holyoake T, Jiang X, Eaves C, Eaves A. Isolation of a highly quiescent subpopulation of primitive leukemic cells in chronic myeloid leukemia. Blood. 1999;94(6):2056-2064.PubMedGoogle Scholar
  16. 16.
    Miyamoto T, Weissman IL, Akashi K. AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation. Proc Natl Acad Sci USA. 2000;97(13):7521–7526.CrossRefPubMedGoogle Scholar
  17. 17.
    Hope KJ, Jin L, Dick JE. Acute myeloid leukemia originates from a hierarchy of leukemic stem cell classes that differ in self-renewal capacity. Nat Immunol. 2004;5(7):738–743.CrossRefPubMedGoogle Scholar
  18. 18.
    Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003;100(7):3983–3988.CrossRefPubMedGoogle Scholar
  19. 19.
    Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003;63(18):5821–5828.PubMedGoogle Scholar
  20. 20.
    Singh SK, Hawkins C, Clarke ID, et al. Identification of human brain tumour initiating cells. Nature. 2004;432(7015):396–401.CrossRefPubMedGoogle Scholar
  21. 21.
    O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445(7123):106–110.CrossRefPubMedGoogle Scholar
  22. 22.
    Dalerba P, Dylla SJ, Park IK, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA. 2007;104(24):10158–10163.CrossRefPubMedGoogle Scholar
  23. 23.
    Li C, Heidt DG, Dalerba P, et al. Identification of pancreatic cancer stem cells. Cancer Res. 2007;67(3):1030–1037.CrossRefPubMedGoogle Scholar
  24. 24.
    Prince ME, Sivanandan R, Kaczorowski A, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA. 2007;104(3):973–978.CrossRefPubMedGoogle Scholar
  25. 25.
    Bao S, Wu Q, McLendon RE, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006;444(7120):756–760.CrossRefPubMedGoogle Scholar
  26. 26.
    Espey DK, Wu XC, Swan J, et al. Annual report to the nation on the status of cancer, 1975-2004, featuring cancer in American Indians and Alaska Natives. Cancer. 2007;110(10):2119–2152.CrossRefPubMedGoogle Scholar
  27. 27.
    Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58(2):71–96.CrossRefPubMedGoogle Scholar
  28. 28.
    Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al. Identification and expansion of human colon-cancer-initiating cells. Nature. 2007;445(7123):111–115.CrossRefPubMedGoogle Scholar
  29. 29.
    Cox CV, Martin HM, Kearns PR, Virgo P, Evely RS, Blair A. Characterization of a progenitor cell population in childhood T-cell acute lymphoblastic leukemia. Blood. 2007;109(2):674–682.CrossRefPubMedGoogle Scholar
  30. 30.
    Schatton T, Murphy GF, Frank NY, et al. Identification of cells initiating human melanomas. Nature. 2008;451(7176):345–349.CrossRefPubMedGoogle Scholar
  31. 31.
    Eramo A, Lotti F, Sette G, et al. Identification and expansion of the tumorigenic lung cancer stem cell population. Cell Death Differ. 2008;15(3):504–514.CrossRefPubMedGoogle Scholar
  32. 32.
    Matsui W, Wang Q, Barber JP, et al. Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res. 2008;68(1):190–197.CrossRefPubMedGoogle Scholar
  33. 33.
    Traggiai E, Chicha L, Mazzucchelli L, et al. Development of a human adaptive immune system in cord blood cell-transplanted mice. Science. 2004;304(5667):104–107.CrossRefPubMedGoogle Scholar
  34. 34.
    Clarkson B, Strife A, Fried J, et al. Studies of cellular proliferation in human leukemia. IV. Behavior of normal hematopoietic cells in 3 adults with acute leukemia given continuous infusions of 3H-thymidine for 8 or 10 days. Cancer. 1970;26(1):1–19.CrossRefPubMedGoogle Scholar
  35. 35.
    Ellisen LW, Bird J, West DC, et al. TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell. 1991;66(4):649–661.CrossRefPubMedGoogle Scholar
  36. 36.
    Lessard J, Sauvageau G. Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature. 2003;423(6937):255–260.CrossRefPubMedGoogle Scholar
  37. 37.
    Lu D, Zhao Y, Tawatao R, et al. Activation of the Wnt signaling pathway in chronic lymphocytic leukemia. Proc Natl Acad Sci USA. 2004;101(9):3118–3123.CrossRefPubMedGoogle Scholar
  38. 38.
    Peacock CD, Wang Q, Gesell GS, et al. Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma. Proc Natl Acad Sci USA. 2007;104(10):4048–4053.CrossRefPubMedGoogle Scholar
  39. 39.
    Pear WS, Aster JC, Scott ML, et al. Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles. J Exp Med. 1996;183(5):2283–2291.CrossRefPubMedGoogle Scholar
  40. 40.
    Yang F, Zeng Q, Yu G, Li S, Wang CY. Wnt/beta-catenin signaling inhibits death receptor-mediated apoptosis and promotes invasive growth of HNSCC. Cell Signal. 2006;18(5):679–687.CrossRefPubMedGoogle Scholar
  41. 41.
    Zheng X, Beissert T, Kukoc-Zivojnov N, et al. Gamma-catenin contributes to leukemogenesis induced by AML-associated translocation products by increasing the self-renewal of very primitive progenitor cells. Blood. 2004;103(9):3535–3543.CrossRefPubMedGoogle Scholar
  42. 42.
    Herschman HR. PET reporter genes for noninvasive imaging of gene therapy, cell tracking and transgenic analysis. Crit Rev Oncol Hematol. 2004;51(3):191–204.CrossRefPubMedGoogle Scholar
  43. 43.
    Majeti R, Park CY, Weissman IL. Identification of a hierarchy of multipotent hematopoietic progenitors in human cord blood. Cell Stem Cell. 2007;1(6):635–645.CrossRefPubMedGoogle Scholar
  44. 44.
    Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science. 1990;247(4944):824–830.CrossRefPubMedGoogle Scholar
  45. 45.
    Elefanty AG, Hariharan IK, Cory S. bcr-abl, the hallmark of chronic myeloid leukaemia in man, induces multiple haemopoietic neoplasms in mice. EMBO J. 1990;9(4):1069–1078.PubMedGoogle Scholar
  46. 46.
    Hariharan IK, Harris AW, Crawford M, et al. A bcr-v-abl oncogene induces lymphomas in transgenic mice. Mol Cell Biol. 1989;9(7):2798–2805.PubMedGoogle Scholar
  47. 47.
    Heisterkamp N, Jenster G, ten Hoeve J, Zovich D, Pattengale PK, Groffen J. Acute leukaemia in bcr/abl transgenic mice. Nature. 1990;344(6263):251–253.CrossRefPubMedGoogle Scholar
  48. 48.
    Kelliher MA, McLaughlin J, Witte ON, Rosenberg N. Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL. Proc Natl Acad Sci USA. 1990;87(17):6649–6653.CrossRefPubMedGoogle Scholar
  49. 49.
    Nowell PC. The minute chromosome (Phl) in chronic granulocytic leukemia. Blut. 1962;8:65–66.CrossRefPubMedGoogle Scholar
  50. 50.
    Krivtsov AV, Twomey D, Feng Z, et al. Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature. 2006;442(7104):818–822.CrossRefPubMedGoogle Scholar
  51. 51.
    Somervaille TC, Cleary ML. Identification and characterization of leukemia stem cells in murine MLL-AF9 acute myeloid leukemia. Cancer Cell. 2006;10(4):257–268.CrossRefPubMedGoogle Scholar
  52. 52.
    Weissman I. Stem cell research: paths to cancer therapies and regenerative medicine. JAMA. 2005;294(11):1359–1366.CrossRefPubMedGoogle Scholar
  53. 53.
    Passegue E, Jamieson CH, Ailles LE, Weissman IL. Normal and leukemic hematopoiesis: are leukemias a stem cell disorder or a reacquisition of stem cell characteristics? Proc Natl Acad Sci USA. 2003;100(Suppl 1):11842–11849.CrossRefPubMedGoogle Scholar
  54. 54.
    Jamieson CH, Weissman IL, Passegue E. Chronic versus acute myelogenous leukemia: a question of self-renewal. Cancer Cell. 2004;6(6):531–533.PubMedGoogle Scholar
  55. 55.
    Huntly BJ, Shigematsu H, Deguchi K, et al. MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell. 2004;6(6):587–596.CrossRefPubMedGoogle Scholar
  56. 56.
    Passegue E, Wagner EF, Weissman IL. JunB deficiency leads to a myeloproliferative disorder arising from hematopoietic stem cells. Cell. 2004;119(3):431–443.CrossRefPubMedGoogle Scholar
  57. 57.
    Steidl U, Rosenbauer F, Verhaak RG, et al. Essential role of Jun family transcription factors in PU.1 knockdown-induced leukemic stem cells. Nat Genet. 2006;38(11):1269–1277.CrossRefPubMedGoogle Scholar
  58. 58.
    Yilmaz OH, Valdez R, Theisen BK, et al. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature. 2006;441(7092):475–482.CrossRefPubMedGoogle Scholar
  59. 59.
    Morrison SJ, Weissman IL. The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity. 1994;1(8):661–673.CrossRefPubMedGoogle Scholar
  60. 60.
    Rossi DJ, Bryder D, Zahn JM, et al. Cell intrinsic alterations underlie hematopoietic stem cell aging. Proc Natl Acad Sci USA. 2005;102(26):9194–9199.CrossRefPubMedGoogle Scholar
  61. 61.
    Kondo M, Weissman IL, Akashi K. Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell. 1997;91(5):661–672.CrossRefPubMedGoogle Scholar
  62. 62.
    Akashi K, Traver D, Miyamoto T, Weissman IL. A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature. 2000;404(6774):193–197.CrossRefPubMedGoogle Scholar
  63. 63.
    Na Nakorn T, Traver D, Weissman IL, Akashi K. Myeloerythroid-restricted progenitors are sufficient to confer radioprotection and provide the majority of day 8 CFU-S. J Clin Invest. 2002;109(12):1579–1585.PubMedGoogle Scholar
  64. 64.
    Manz MG, Miyamoto T, Akashi K, Weissman IL. Prospective isolation of human clonogenic common myeloid progenitors. Proc Natl Acad Sci USA. 2002;99(18):11872–11877.CrossRefPubMedGoogle Scholar
  65. 65.
    Konopka JB, Watanabe SM, Witte ON. An alteration of the human c-abl protein in K562 leukemia cells unmasks associated tyrosine kinase activity. Cell. 1984;37(3):1035–1042.CrossRefPubMedGoogle Scholar
  66. 66.
    Nelson WJ, Nusse R. Convergence of Wnt, beta-catenin, and cadherin pathways. Science. 2004;303(5663):1483-1487.CrossRefPubMedGoogle Scholar
  67. 67.
    Reya T, Duncan AW, Ailles L, et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature. 2003;423(6938):409–414.CrossRefPubMedGoogle Scholar
  68. 68.
    Willert K, Brown JD, Danenberg E, et al. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature. 2003;423(6938):448–452.CrossRefPubMedGoogle Scholar
  69. 69.
    Lustig B, Jerchow B, Sachs M, et al. Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors. Mol Cell Biol. 2002;22(4):1184–1193.CrossRefPubMedGoogle Scholar
  70. 70.
    Mostowska A, Biedziak B, Jagodzinski PP. Axis inhibition protein 2 (AXIN2) polymorphisms may be a risk factor for selective tooth agenesis. J Hum Genet. 2006;51(3):262–266.CrossRefPubMedGoogle Scholar
  71. 71.
    Cong F, Varmus H. Nuclear-cytoplasmic shuttling of Axin regulates subcellular localization of beta-catenin. Proc Natl Acad Sci USA. 2004;101(9):2882–2887.CrossRefPubMedGoogle Scholar
  72. 72.
    Pospisil H, Herrmann A, Butherus K, Pirson S, Reich JG, Kemmner W. Verification of predicted alternatively spliced Wnt genes reveals two new splice variants (CTNNB1 and LRP5) and altered Axin-1 expression during tumour progression. BMC Genomics. 2006;7:148.CrossRefPubMedGoogle Scholar
  73. 73.
    Abrahamsson AE, Geron I, Gotlib J, et al. Glycogen synthase kinase 3beta missplicing contributes to leukemia stem cell generation. Proc Natl Acad Sci USA. 2009;106(10):3925–3929.CrossRefPubMedGoogle Scholar
  74. 74.
    Guzman ML, Neering SJ, Upchurch D, et al. Nuclear factor-kappaB is constitutively activated in primitive human acute myelogenous leukemia cells. Blood. 2001;98(8):2301–2307.CrossRefPubMedGoogle Scholar
  75. 75.
    Jamieson CH, Gotlib J, Durocher JA, et al. The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation. Proc Natl Acad Sci USA. 2006;103(16):6224–6229.CrossRefPubMedGoogle Scholar
  76. 76.
    Geron I, Abrahamsson AE, Barroga CF, et al. Selective inhibition of JAK2-driven erythroid differentiation of polycythemia vera progenitors. Cancer Cell. 2008;13(4):321–330.CrossRefPubMedGoogle Scholar
  77. 77.
    Klug CA, Morrison SJ, Masek M, Hahm K, Smale ST, Weissman IL. Hematopoietic stem cells and lymphoid progenitors express different Ikaros isoforms, and Ikaros is localized to heterochromatin in immature lymphocytes. Proc Natl Acad Sci USA. 1998;95(2):657–662.CrossRefPubMedGoogle Scholar
  78. 78.
    Jorgensen HG, Holyoake TL. Characterization of cancer stem cells in chronic myeloid leukaemia. Biochem Soc Trans. 2007;35(Pt 5):1347–1351.PubMedGoogle Scholar
  79. 79.
    Bao F, Polk P, Nordberg ML, et al. Comparative gene expression analysis of a chronic myelogenous leukemia cell line resistant to cyclophosphamide using oligonucleotide arrays and response to tyrosine kinase inhibitors. Leuk Res. 2007;31(11):1511–1520.CrossRefPubMedGoogle Scholar
  80. 80.
    Rich JN, Bao S. Chemotherapy and cancer stem cells. Cell Stem Cell. 2007;1(4):353–355.CrossRefPubMedGoogle Scholar
  81. 81.
    Harrison CN, Campbell PJ, Buck G, et al. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med. 2005;353(1):33–45.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Isabel G. Newton
    • 1
  • Catriona H. M. Jamieson
    • 2
  1. 1.Research Resident, Radiology DepartmentUniversity of California San Diego Medical CenterSan DiegoUSA
  2. 2.Division of Hematology-Oncology, Department of MedicineUniversity of CaliforniaSan Diego, La JollaUSA

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