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Bone Marrow Niche and Leukemia

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Book cover Cancer Stem Cells

Part of the book series: Springer Series on Biofilms ((SCHERING FOUND,volume 2006/5))

Abstract

Mounting evidence indicates that human cancers may originate from malignant transformation of stem cells. The most convincing proof is found in acute myeloid leukemia, where only a small subset of slowly dividing cells was able to induce transplantable acute myeloid leukemia. Normal hematopoietic stem cells (HSC) are characterized by their unlimited ability to self-renew, give rise to a multitude of cells that exhibit more differentiated features, and show slow division kinetics. Using human HSC and mesenchymal stromal cells (MSC) as models, we and others have demonstrated the vital role of the cellular niche in maintaining the self-renewing capacity, that is, “stemness” of HSC. Without direct contact with the cellular niche, HSC tend to differentiate and lose their stemness. Similar to their normal counterparts, leukemia stem cells divide slowly and maintain their self-renewal capacity through interaction with the niche. As a consequence, they are resistant to conventional chemotherapy strategies that target rapidly dividing cells. Thus it is of utmost importance to understand the interaction between cellular niche and normal HSC as well as between leukemia stem cells and the niche to provide a basis for more efficient treatment strategies.

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References

  • Avigdor A, Goichberg P, Shivtiel S, Dar A, Peled A, Samira S, Kollet O, Hershkoviz R, Alon R, Hardan I, Ben-Hur H, Naor D, Nagler A, Lapidot T (2004) CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/progenitor cells to bone marrow. Blood 103:2981–2989

    Article  CAS  PubMed  Google Scholar 

  • Becker A, McCulloch EA, Till JE (1963) Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 197:452

    Article  CAS  PubMed  Google Scholar 

  • Berardi AC, Wang A, Levina JD, Lopez P, Scadden DT (1995) Functional isolation and characterization of human hematopoietic stem cells. Science 267:104–108

    Article  CAS  PubMed  Google Scholar 

  • Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737

    Article  CAS  PubMed  Google Scholar 

  • Calvi LM, Adams GB, Weibrecht KM, et al (2003) Osteoblastic cells regulate the hematopoietic progenitor cell niche. Nature 425:841–846

    Article  CAS  PubMed  Google Scholar 

  • Campisi J (2005) Suppressing cancer: the importance of being senescent. Science 309:886–887

    Article  CAS  PubMed  Google Scholar 

  • Danet GH, Luongo JL, Butler G, et al (2002) C1qRp defines a new human stem cell population with hematopoietic and hepatic potential. Proc Natl Acad Sci USA 99:10441–10445

    Article  CAS  PubMed  Google Scholar 

  • Francis K, Ramakrishna R, Holloway W, Palsson BO (1998) Two new pseudopod morphologies displayed by the human hematopoietic KG1a progenitor cell line and by primary human CD34+ cells. Blood 92:3616–3623

    CAS  PubMed  Google Scholar 

  • Francis K, Palsson B, Donahue J, Fong S, Carrier E (2002) Murine Sca-1+/Lin− cells and human KG1a cells exhibit multiple pseudopod morphologies during migration. Exp Hematol 30:460–463

    Article  CAS  PubMed  Google Scholar 

  • Frimberger AE, McAulife CI, Werme KA, Tuft RA, Fogarty KE, Benoit BO, Dooner MS, Quesenberry PJ (2001) The fleet feet of haematopoietic stem cells: rapid motility, interaction and proteopodia. Br J Haematol 112:644–654

    Article  CAS  PubMed  Google Scholar 

  • Frühauf S, Srbic K, Seggewiss R, Topaly J, Ho AD (2002) Functional characterization of podia formation in normal and malignant hematopoietic cells. J Leukoc Biol 71:425–432

    Google Scholar 

  • Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F, Vescovi A (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64:7011–7021

    Article  CAS  PubMed  Google Scholar 

  • Giebel B, Zhang T, Beckmann J, Spanholtz J, Wernet P, Ho AD, Punzel M (2006) Primitive human hematopoietic cells give rise to differentially specified daughter cells upon their initial cell division. Blood 107:2146–2152

    Article  CAS  PubMed  Google Scholar 

  • Gottschling S, Saffrich R, Seckinger A, Krause U, Horsch K, Miesala K, Ho AD (2007) Human mesenchymal stroma cells regulate initial self-renewing divisions of hematopoietic progenitor cells by a β1-integrin-dependent mechanism. Stem Cells 25:798–806

    Article  CAS  PubMed  Google Scholar 

  • Ho AD (2005) Kinetics and symmetry of divisions of hematopoietic stem cells. Exp Hematol 33:1–8

    Article  CAS  PubMed  Google Scholar 

  • Ho AD, Punzel M (2003) Hematopoietic stem cells: can old cells learn new tricks? J Leukoc Biol 73:547–555

    Article  CAS  PubMed  Google Scholar 

  • Holloway W, Martinez AR, OH DJ, Francis K, Ramakrishna R, Palsson BO (1999) Key adhesion molecules are present on long podia extended by hematopoietic cells. Cytometry 37:171–177

    Google Scholar 

  • Huang S, Law P, Francis K, Palsson BO, Ho AD (1999) Symmetry of initial cell divisions among primitive hematopoietic progenitors is independent of ontogenic age and regulatory molecule. Blood 94:2595–2604

    CAS  PubMed  Google Scholar 

  • Huntly BJ, Gilliland DG (2005) Leukaemia stem cells and the evolution of cancer-stem-cell research. Nat Rev Cancer 5:311–321

    Article  CAS  PubMed  Google Scholar 

  • Ivanova NB, Dimos JT, Schaniel C, Hackney JA, Moore KA, Lemischka IR (2002) A stem cell molecular signature. Science 298:601–604

    Article  CAS  PubMed  Google Scholar 

  • Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE (2006) Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med 12:1167–1174

    Article  PubMed  Google Scholar 

  • Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE (1994) A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367:645–648

    Article  CAS  PubMed  Google Scholar 

  • Metcalf D (1998) Lineage commitment and maturation in hematopoietic cells: the case for extrinsic regulation. Blood 29:345

    Google Scholar 

  • Mueller MM, Fusenig NE (2004) Friends or foes—bipolar effects of the tumour stroma in cancer. Nat Rev Cancer 4:839–849

    Article  CAS  PubMed  Google Scholar 

  • Owens DM, Watt FM (2003) Contribution of stem cells and differentiated cells to epidermal tumours. Nat Rev Cancer 3:444–451

    Article  CAS  PubMed  Google Scholar 

  • Pardal R, Clarke MF, Morrison SJ (2003) Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 3:895–902

    Article  CAS  PubMed  Google Scholar 

  • Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, Pilotti S (2005) Pierotti MA, Daidone MG. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res 65:5506–5511

    Article  CAS  PubMed  Google Scholar 

  • Punzel M, Zhang T, Liu D, Eckstein V, Ho AD (2002) Functional analysis of initial cell divisions defines the subsequent fate of individual human CD34+CD38− cells. Exp Hematol 30:464–472

    Article  CAS  PubMed  Google Scholar 

  • Punzel M, Liu D, Zhang T, Eckstein V, Miesala K, Ho AD (2003) The symmetry of initial divisions of human hematopoietic progenitors is altered only by the cellular microenvironment. Exp Hematol 31:339–347

    Article  PubMed  Google Scholar 

  • Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA (2002) “Stemness”: transcriptional profiling of embryonic and adult stem cells. Science 298:597–600

    Article  CAS  PubMed  Google Scholar 

  • Siminovitch L, McCulloch EA, Till JE (1963) The distribution of colony-forming cells among spleen colonies. J Cell Comp Physiol 62:327–336

    Article  CAS  Google Scholar 

  • Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432:396–401

    Article  CAS  PubMed  Google Scholar 

  • Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, Choi D, Li HI, Eaves CJ (2006) Purification and unique properties of mammary epithelial stem cells. Nature 439:993–997

    CAS  PubMed  Google Scholar 

  • Verfaillie CM (1993) Soluble factor(s) produced by human bone marrow stroma increase cytokine-induced proliferation and maturation of primitive hematopoietic progenitors while preventing their terminal differentiation. Blood 82:2045

    CAS  PubMed  Google Scholar 

  • Wagner W, Ansorge A, Wirkner U, Eckstein V, Schwager C, Blake J, Miesala K, Selig J, Saffrich R, Ansorge W, Ho AD (2004) Molecular evidence for stem cell function of the slow-dividing fraction among human hematopoietic progenitor cells by genome-wide analysis. Blood 104:675–686

    Article  CAS  PubMed  Google Scholar 

  • Wagner W, Saffrich R, Wirkner U, Eckstein V, Blake J, Ansorge A, Schwager C, Wein F, Miesala K, Ansorge W, Ho AD (2005) Hematopoietic progenitor cells and cellular microenvironment—behavioral and molecular changes upon interaction. Stem Cells 23:1180–1191

    Article  CAS  PubMed  Google Scholar 

  • Wagner W, Wein F, Roderburg C, Saffrich R, Faber A, Krause U, Schubert M, Benes V, Eckstein V, Maul H, Ho AD (2007) Adhesion of hematopoietic progenitor cells to human mesenchymal stem cells as a model for cell-cell interaction. Exp. Hematol. 35:314–325

    Article  CAS  PubMed  Google Scholar 

  • Weissman IL (2000) Translating stem and progenitor cell biology to the clinic: barriers and opportunities. Science 287:1442–1446

    Article  CAS  PubMed  Google Scholar 

  • Wuchter P, Boda J, Grund C, Kuhn C, Krause U, Eckstein V, Gottschling S, Franke WW, Ho AD (2003) A novel type of cell–cell connections in mesenchymal stem cells. Blood 102:1309

    Google Scholar 

  • Wuchter P, Boda-Heggemann J, Straub BK, Grund C, Kuhn C, Krause U, Seckinger A, Peitsch WK, Ho AD, Franke WW (2007) Processus and recessus adhäerentes: giant adherens cell junction systems connect and attract human mesenchymal stem cells. Cell Tissue Research 328:499–514

    Article  PubMed  Google Scholar 

  • Yamashita QM, Jones DL, Fuller MG (2003) Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome. Science301:1447–1550

    Article  Google Scholar 

  • Young JC, Varma A, DiGiusto D, Backer MP (1996) Retention of quiescent hematopoietic cells with high proliferative potential during ex vivo stem cell culture. Blood 87:545

    CAS  PubMed  Google Scholar 

  • Zhang J, Niu C, Ye L, et al (2003) Identification of hematopoietic progenitor cells niche and control of the niche size. Nature 425:836–841

    Article  CAS  PubMed  Google Scholar 

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Correspondence to A. D. Ho .

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O.D. Wiestler B. Haendler D. Mumberg

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© 2007 Springer-Verlag

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Ho, A.D., Wagner, W. (2007). Bone Marrow Niche and Leukemia. In: Wiestler, O., Haendler, B., Mumberg, D. (eds) Cancer Stem Cells. Springer Series on Biofilms, vol 2006/5. Springer, Berlin, Heidelberg. https://doi.org/10.1007/2789_2007_048

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  • DOI: https://doi.org/10.1007/2789_2007_048

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-70852-0

  • Online ISBN: 978-3-540-70853-7

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