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Spotlight on Hematopoietic Stem Cells: Looking Beyond Dogma

Introduction

Leukemia volume 15, pages 1677–1680 (2001)Cite this article

Some of the long-established dogma concerning normal hematopoietic and leukemic stem cell phenotype and function have been questioned in the past few years. As a result, recent publications have been exciting and presentations at Hematology meetings have sometimes been highly controversial. This section will address some of the new cutting-edge experimentation that is going on in the field, with special attention to novel, well-documented evidence that alters our perception of old stem cell dogma.

An initial topic that has been recently reviewed in this area is that evidence now exists to support the presence of both murine and human hematopoietic stem cells that lack expression of the CD34 marker (reviewed in Refs 1,2,3). There appears to be a degree of reversibility of expression of CD34 at the stem cell surface, in both murine4 and human stem cells.5 The appearance and disappearance of the cell surface protein could complicate CD34+ cell immunoisolation methods that are designed to debulk or T cell deplete bone marrow or peripheral blood products for transplantation. However, the reversibility data suggests that the CD34+ stem cell pool may be able to generate the CD34− pool, and vice versa. Whether the two pools have different generative potentials, either in the number or in the type of progeny that they produce, remains to be determined.

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References

  1. Goodell MA . Introduction: focus on hematology CD34(+) or CD34(−): does it really matter? Blood 1999 94: 2545–2547

    CAS  PubMed  Google Scholar 

  2. Lemischka I . The power of stem cells reconsidered? Proc Natl Acad Sci USA 1999 96: 14193–14195

    Article  CAS  Google Scholar 

  3. Dao MA, Nolta JA . CD34: to select or not to select? That is the question Leukemia 2000 14: 773–776

    Article  CAS  Google Scholar 

  4. Sato T, Laver JH, Ogawa M . Reversible expression of CD34 by murine hematopoietic stem cells Blood 1999 94: 2548–2554

    CAS  Google Scholar 

  5. Dao M, Nolta J . Reversibility of CD34 expression on human stem cells that retain the capacity for secondary multilineage reconstitution Blood 2000 96: 581a

    Google Scholar 

  6. Bhatia M, Bonnet D, Kapp U, Wang JC, Murdoch B, Dick JE . Quantitative analysis reveals expansion of human hematopoietic repopulating cells after short-term ex vivo culture J Exp Med 1997 186: 619–624

    Article  CAS  Google Scholar 

  7. Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC . Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo J Exp Med 1996 183: 1797–1806

    Article  CAS  Google Scholar 

  8. Goodell MA, Rosenzweig M, Kim H, Marks DF, DeMaria M, Paradis G, Grupp SA, Sieff CA, Mulligan RC, Johnson RP . Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species Nat Med 1997 3: 1337–1345

    Article  CAS  Google Scholar 

  9. Storms RW, Goodell MA, Fisher A, Mulligan RC, Smith C . Hoechst dye efflux reveals a novel CD7(+)CD34(−) lymphoid progenitor in human umbilical cord blood Blood 2000 96: 2125–2133

    CAS  Google Scholar 

  10. Lagasse E, Connors H, Al-Dhalimy M, Reitsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissman IL, Grompe M . Purified hematopoietic stem cells can differentiate into hepatocytes in vivo Nat Med 2000 6: 1229–1234

    Article  CAS  Google Scholar 

  11. Bowers E, Tamaki S, Coward A, Kaneshima H, Chao CC . Differing functional recovery of donor-derived immune cells after purified haploidentical and fully mismatched hematopoietic stem cell transplantation in mice Exp Hematol 2000 28: 1481–1489

    Article  CAS  Google Scholar 

  12. Uchida N, Friera AM, He D, Reitsma MJ, Tsukamoto AS, Weissman IL . Hydroxyurea can be used to increase mouse (−kit+Thy-1. 1(lo)Lin-/loSca-1(+) hematopoietic cell number and frequency in cell cycle in vivo Blood 1997 90: 4354–4362

    CAS  PubMed  Google Scholar 

  13. Uchida N, Tsukamoto A, He D, Friera AM, Scollay R, Weissman IL . High doses of purified stem cells cause early hematopoietic recovery in syngeneic and allogeneic hosts J Clin Invest 1998 101: 961–966

    Article  CAS  Google Scholar 

  14. Jackson KA, Mi T, Goodell MA . Hematopoietic potential of stem cells isolated from murine skeletal muscle Proc Natl Acad Sci USA 1999 96: 14482–14486

    Article  CAS  Google Scholar 

  15. Gussoni E, Soneoka Y, Strickland CD, Buzney EA, Khan MK, Flint AF, Kunkel LM, Mulligan RC . Dystrophin expression in the mdx mouse restored by stem cell transplantation Nature 1999 401: 390–394

    CAS  Google Scholar 

  16. Orlic D, Kajstura J, Chimenti S, Jakoniak I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P . Bone marrow cells regenerate infarcted myocardium Nature 2001 410: 701–705

    Article  CAS  Google Scholar 

  17. Nolta JA, Dao MA, Wells S, Smogorzewska EM, Kohn DB . Transduction of pluripotent human hematopoietic stem cells demonstrated by clonal analysis after engraftment in immune-deficient mice Proc Natl Acad Sci USA 1996 93: 2414–2419

    Article  CAS  Google Scholar 

  18. Theise ND, Nimmakayalu M, Gardner R, Illei PB, Morgan G, Teperman L, Henegariu O, Krause DS . Liver from bone marrow in humans Hepatology 2000 32: 11–16

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  21. Blair A, Hogge DE, Sutherland HJ . Most acute myeloid leukemia progenitor cells with long-term proliferative ability in vitro and in vivo have the phenotype CD34(+)/CD71(−)/HLA-DR Blood 1998 92: 4325–4335

    CAS  Google Scholar 

  22. 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: 3104–3112

    CAS  Google Scholar 

  23. Blair A, Sutherland HJ . Primitive acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo lack surface expression of c-kit (CD117) Exp Hematol 2000 28: 660–671

    Article  CAS  Google Scholar 

  24. Jordan CT, Upchurch D, Szilvassy SJ, Guzman ML, Howard DS, Pettigrew AL, Meyerrose T, Rossi R, Grimes B, Rizzieri DA, Luger SM, Phillips GL . The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells Leukemia 2000 14: 1777–1784

    Article  CAS  Google Scholar 

  25. Guzman ML NS, Upchurch D, Grimes B, Howard DS, Rizzieri DA, Luger SM, Jordan CT . NF-kB is constitutively activated in primitive human acute myelogenous leukemia cells Blood 2001 (in press)

  26. Guzman ML, Upchurch D, Grimes B, Howard DS, Rizzieri DA, Luger SM, Phillips GL, Jordan CT . Expression of tumor-suppressor genes interferon regulatory factor 1 and death-associated protein kinase in primitive acute myelogenous leukemia cells Blood 2001 97: 2177–2179

    Article  CAS  Google Scholar 

  27. Jiang X, Lopez A, Holyoake T, Eaves A, Eaves C . Autocrine production and action of IL-3 and granulocyte colony-stimulatingfactor in chronic myeloid leukemia Proc Natl Acad Sci USA 1999 96: 12804–12809

    Article  CAS  Google Scholar 

  28. Jiang X, Fujisaki T, Nicolini F, Berger M, Holyoake T, Eisterer W, Eaves C, Eaves A . Autonomous multi-lineage differentiation in vitro of primitive CD34+ cells from patients with chronic myeloid leukemia Leukemia 2000 14: 1112–1121

    Article  CAS  Google Scholar 

  29. Holyoake TL, Jiang X, Jorgensen HG, Graham S, Alcorn MJ, Laird C, Eaves AC, Eaves CJ . Primitive quiescent leukemic cells from patients with chronic myeloid leukemia spontaneously initiate factor-independent growth in vitro in association with up-regulation of expression of interleukin-3 Blood 2001 97: 720–728

    Article  CAS  Google Scholar 

  30. 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: 2056–2064

    CAS  Google Scholar 

  31. Rosu-Myles M, Gallacher L, Murdoch B, Hess DA, Keeney M, Kelvin D, Dale L, Ferguson SS, Wu D, Fellows F, Bhatia M . The human hematopoietic stem cell compartment is heterogeneous for CXCR4 expression Proc Natl Acad Sci USA 2000 97: 14626–14631

    Article  CAS  Google Scholar 

  32. Peled A, Petit I, Kollet O, Magid M, Ponomaryov T, Byk T, Nagler A, Ben-Hur H, Many A, Shultz L, Lider O, Alon R, Zipori D, Lapidot T . Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4 Science 1999 283: 845–848

    Article  CAS  Google Scholar 

  33. Kollet O, Spiegel A, Peled A, Petit I, Byk T, Hershkoviz R, Guetta E, Barkai G, Nagler A, Lapidot T . Rapid and efficient homing of human CD34(+)CD38(−/low) CXCR4(+) stem and progenitor cells to the bone marrow and spleen of NOD/SCID and NOD/SCID/B2m(null) mice Blood 2001 97: 3283–3291

    Article  CAS  Google Scholar 

  34. Orschell-Traycoff CM, Hiatt K, Dagher RN, Rice S, Yoder MC, Srour EF . Homing and engraftment potential of Sca-1(+)lin(−) cells fractionated on the basis of adhesion molecule expression and position in cell cycle Blood 2000 96: 1380–1387

    CAS  PubMed  Google Scholar 

  35. Becker PS, Nilsson SK, Li Z, Berrios VM, Dooner MS, Cooper CL, Hsieh CC, Quesenberry PJ . Adhesion receptor expression by hematopoietic cell lines and murine progenitors: modulation by cytokines and cell cycle status Exp Hematol 1999 27: 533–541

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Rob Ploemacher for his help and advice on the organization of the spotlight section.

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  1. Children's Hospital of Los Angeles, Los Angeles, CA, USA

    JA Nolta & CT Jordan

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Nolta, J., Jordan, C. Introduction. Leukemia 15, 1677–1680 (2001). https://doi.org/10.1038/sj.leu.2402254

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