Experimental Hematology
Volume 37, Issue 12 , Pages 1423-1434 , December 2009

Aldehyde dehydrogenase activity among primary leukemia cells is associated with stem cell features and correlates with adverse clinical outcomes

  • Dan Ran

      Affiliations

    • Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
    • Drs. Ran and Schubert contributed equally to this work.
    • ,
  • Mario Schubert

      Affiliations

    • Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
    • Drs. Ran and Schubert contributed equally to this work.
    • ,
  • Larissa Pietsch

      Affiliations

    • Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
    • ,
  • Isabel Taubert

      Affiliations

    • Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
    • ,
  • Patrick Wuchter

      Affiliations

    • Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
    • ,
  • Volker Eckstein

      Affiliations

    • Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
    • ,
  • Thomas Bruckner

      Affiliations

    • Department of Biometry, University of Heidelberg, Heidelberg, Germany
    • ,
  • Margot Zoeller

      Affiliations

    • Department of Surgery, Section for Tumor Cell Biology, University of Heidelberg, Heidelberg, Germany
    • ,
  • Anthony D. Ho

      Affiliations

    • Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
    • Corresponding Author InformationOffprint requests to: Anthony D. Ho, M.D., Department of Internal Medicine V, Im Neuenheimer Feld 410, Heidelberg 69120, Germany

Received 10 August 2009 ,Revised 5 October 2009 ,Accepted 5 October 2009.

References 

  1. Sutherland HJ, Blair A, Zapf RW. Characterization of a hierarchy in human acute myeloid leukemia progenitor cells. Blood. 1996;87:4754–4761
  2. Huntly BJ, Gilliland DG. Leukaemia stem cells and the evolution of cancer-stem-cell research. Nat Rev Cancer. 2005;5:311–321
  3. Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367:645–648
  4. 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
  5. Pearce DJ, Taussig D, Zibara K, et al. AML engraftment in the NOD/SCID assay reflects the outcome of AML: implications for our understanding of the heterogeneity of AML. Blood. 2006;107:1166–1173
  6. van Rhenen A, Feller N, Kelder A, et al. High stem cell frequency in acute myeloid leukemia at diagnosis predicts high minimal residual disease and poor survival. Clin Cancer Res. 2005;11:6520–6527
  7. 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
  8. Brendel C, Mohr B, Schimmelpfennig C, et al. Detection of cytogenetic aberrations both in CD90 (Thy-1)-positive and (Thy-1)-negative stem cell (CD34) subfractions of patients with acute and chronic myeloid leukemias. Leukemia. 1999;13:1770–1775
  9. Taussig DC, Pearce DJ, Simpson C, et al. Hematopoietic stem cells express multiple myeloid markers: implications for the origin and targeted therapy of acute myeloid leukemia. Blood. 2005;106:4086–4092
  10. Yoshida A, Rzhetsky A, Hsu LC, Chang C. Human aldehyde dehydrogenase gene family. Eur J Biochem. 1998;251:549–557
  11. Duester G. Families of retinoid dehydrogenases regulating vitamin A function: production of visual pigment and retinoic acid. Eur J Biochem. 2000;267:4315–4324
  12. Chu P, Clanton DJ, Snipas TS, et al. Characterization of a subpopulation of colon cancer cells with stem cell-like properties. Int J Cancer. 2009;124:1312–1321
  13. Ucar D, Cogle CR, Zucali JR, et al. Aldehyde dehydrogenase activity as a functional marker for lung cancer. Chem Biol Interact. 2009;178:48–55
  14. Ma S, Chan KW, Lee TK, et al. Aldehyde dehydrogenase discriminates the CD133 liver cancer stem cell populations. Mol Cancer Res. 2008;6:1146–1153
  15. Ginestier C, Hur MH, Charafe-Jauffret E, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1:555–567
  16. Croker AK, Goodale D, Chu J, et al. High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability. J Cell Mol Med. 2008 Aug 4;[Epub ahead of print]
  17. Pearce DJ, Taussig D, Simpson C, et al. Characterization of cells with a high aldehyde dehydrogenase activity from cord blood and acute myeloid leukemia samples. Stem Cells. 2005;23:752–760
  18. Cheung AM, Wan TS, Leung JC, et al. Aldehyde dehydrogenase activity in leukemic blasts defines a subgroup of acute myeloid leukemia with adverse prognosis and superior NOD/SCID engrafting potential. Leukemia. 2007;21:1423–1430
  19. Christ O, Lucke K, Imren S, et al. Improved purification of hematopoietic stem cells based on their elevated aldehyde dehydrogenase activity. Haematologica. 2007;92:1165–1172
  20. Storms RW, Trujillo AP, Springer JB, et al. Isolation of primitive human hematopoietic progenitors on the basis of aldehyde dehydrogenase activity. Proc Natl Acad Sci U S A. 1999;96:9118–9123
  21. Hess DA, Wirthlin L, Craft TP, et al. Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoietic stem cells. Blood. 2006;107:2162–2169
  22. Wang JS, Fang Q, Sun DJ, et al. Genetic modification of hematopoietic progenitor cells for combined resistance to 4-hydroperoxycyclophosphamide, vincristine, and daunorubicin. Acta Pharmacol Sin. 2001;22:949–955
  23. Chute JP, Muramoto GG, Whitesides J, et al. Inhibition of aldehyde dehydrogenase and retinoid signaling induces the expansion of human hematopoietic stem cells. Proc Natl Acad Sci U S A. 2006;103:11707–11712
  24. Haase D, Feuring-Buske M, Konemann S, et al. Evidence for malignant transformation in acute myeloid leukemia at the level of early hematopoietic stem cells by cytogenetic analysis of CD34+ subpopulations. Blood. 1995;86:2906–2912
  25. Krivtsov AV, Twomey D, Feng Z, et al. Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature. 2006;442:818–822
  26. 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;351:657–667
  27. 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;6:587–596
  28. Punzel M, Zhang T, Liu D, Eckstein V, Ho AD. Functional analysis of initial cell divisions defines the subsequent fate of individual human CD34(+)CD38(-) cells. Exp Hematol. 2002;30:464–472
  29. Huang S, Law P, Francis K, Palsson BO, Ho AD. Symmetry of initial cell divisions among primitive hematopoietic progenitors is independent of ontogenic age and regulatory molecules. Blood. 1999;94:2595–2604
  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
  31. Holtz MS, Forman SJ, Bhatia R. Nonproliferating CML CD34+ progenitors are resistant to apoptosis induced by a wide range of proapoptotic stimuli. Leukemia. 2005;19:1034–1041
  32. Elrick LJ, Jorgensen HG, Mountford JC, Holyoake TL. Punish the parent not the progeny. Blood. 2005;105:1862–1866
  33. Misaghian N, Ligresti G, Steelman LS, et al. Targeting the leukemic stem cell: the Holy Grail of leukemia therapy. Leukemia. 2009;23:25–42
  34. Dick JE, Lapidot T. Biology of normal and acute myeloid leukemia stem cells. Int J Hematol. 2005;82:389–396
  35. Ho AD, Wagner W. Bone marrow niche and leukemia. Ernst Schering Found Symp Proc. 2006;125–139
  36. Shiozawa Y, Havens AM, Pienta KJ, Taichman RS. The bone marrow niche: habitat to hematopoietic and mesenchymal stem cells, and unwitting host to molecular parasites. Leukemia. 2008;22:941–950
  37. Wagner W, Wein F, Roderburg C, et al. Adhesion of hematopoietic progenitor cells to human mesenchymal stem cells as a model for cell-cell interaction. Exp Hematol. 2007;35:314–325
  38. Williams RT, den Besten W, Sherr CJ. Cytokine-dependent imatinib resistance in mouse BCR-ABL+, Arf-null lymphoblastic leukemia. Genes Dev. 2007;21:2283–2287
  39. Krause DS, Lazarides K, von Andrian UH, Van Etten RA. Requirement for CD44 in homing and engraftment of BCR-ABL-expressing leukemic stem cells. Nat Med. 2006;12:1175–1180
  40. Jin L, Hope KJ, Zhai Q, Smadja-Joffe F, Dick JE. Targeting of CD44 eradicates human acute myeloid leukemic stem cells. Nat Med. 2006;12:1167–1174
  41. Ailles LE, Gerhard B, Hogge DE. Detection and characterization of primitive malignant and normal progenitors in patients with acute myelogenous leukemia using long-term coculture with supportive feeder layers and cytokines. Blood. 1997;90:2555–2564
  42. Capoccia BJ, Robson DL, Levac KD, et al. Revascularization of ischemic limbs after transplantation of human bone marrow cells with high aldehyde dehydrogenase activity. Blood. 2009;113:5340–5351
  43. Gentry T, Deibert E, Foster SJ, Haley R, Kurtzberg J, Balber AE. Isolation of early hematopoietic cells, including megakaryocyte progenitors, in the ALDH-bright cell population of cryopreserved, banked UC blood. Cytotherapy. 2007;9:569–576
  44. Hess DA, Meyerrose TE, Wirthlin L, et al. Functional characterization of highly purified human hematopoietic repopulating cells isolated according to aldehyde dehydrogenase activity. Blood. 2004;104:1648–1655
  45. Zeng Z, Shi YX, Samudio IJ, et al. Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML. Blood. 2009;113:6215–6224
  46. Vitacolonna M, Schubert M, Herbert N, et al. Improved T and B cell recovery by the transfer of slowly dividing human hematopoietic stem cells. Leukemia Research. In press.
  47. Wagner W, Ansorge A, Wirkner U, et al. Molecular evidence for stem cell function of the slow-dividing fraction among human hematopoietic progenitor cells by genome-wide analysis. Blood. 2004;104:675–686
  48. Magni M, Shammah S, Schiro R, Mellado W, Dalla-Favera R, Gianni AM. Induction of cyclophosphamide-resistance by aldehyde-dehydrogenase gene transfer. Blood. 1996;87:1097–1103

PII: S0301-472X(09)00390-7

doi: 10.1016/j.exphem.2009.10.001

Experimental Hematology
Volume 37, Issue 12 , Pages 1423-1434 , December 2009

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