Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Manuscript
  • Published:

Migratory behavior of leukemic cells from acute myeloid leukemia patients

Leukemia volume 16, pages 650–657 (2002)Cite this article

Abstract

The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR-4 contribute to stem cell homing and may play a role in the trafficking of leukemic cells. Therefore, we analyzed migration across Transwell filters of cells derived from bone marrow (BM) or peripheral blood (PB) from 26 acute myeloid leukemia (AML) patients. The presence of the extracellular matrix protein fibronectin (FN) strongly enhanced the spontaneous and SDF-1-induced migration of leukemic PB and BM cells. No differences in spontaneous, SDF-1-induced migration or CXCR-4 expression were observed between the different AML subtypes. Subsequently, it was determined whether SDF-1 preferentially promoted migration of subsets of leukemic cells. Leukemic cells expressing CD34, CD38 and HLA-DR were preferentially migrating, whereas cells expressing CD14 and CD36 showed diminished migration. Analysis of paired PB and BM samples indicated that significantly higher SDF-1-induced migration was observed in AML for CD34+ BM-derived cells compared to CD34+ PB-derived cells, suggesting a role for SDF-1 in the anchoring of leukemic cells in the BM or other organs. The lower percentage of circulating leukemic blasts in patients with a relatively high level of SDF-1-induced migration also supports this hypothesis. In conclusion, we have shown that primary AML cells are migrating towards SDF-1 independent of the AML subtypes.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  1. Bleul CC, Fuhlbrigge RC, Casasnovas JM, Aiuti A, Springer TA . A highly efficacious lymphocyte chemoattractant, stromal cell-derived factor 1 (SDF-1) J Exp Med 1996 184: 1101–1109

    Article  CAS  PubMed  Google Scholar 

  2. Aiuti A, Webb IJ, Bleul C, Springer TA, Gutierrez-Ramos JC . The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood J Exp Med 1997 185: 111–120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bleul CC, Farzan M, Choe H, Parolin C, Clark-Lewis I, Sodroski J, Springer TA . The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV entry Nature 1996 382: 829–833

    Article  CAS  PubMed  Google Scholar 

  4. Oberlin E, Amara A, Bachelerie F, Bessia C, Virelizier J-L, Arenzana-Seisdedos F, Schwartz O, Heard J-M, Clark-Lewis I, Legler DF, Loetscher M, Baggiolini M, Moser B . The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line adapted HIV-1 Nature 1996 382: 833–835

    Article  CAS  PubMed  Google Scholar 

  5. Loetscher M, Geiser T, O'Reilly T, Zwahlen R, Baggiolini M, Moser B . Cloning of a human seven-transmembrane domain receptor LESTR, that is highly expressed in leukocytes J Biol Chem 1994 269: 232–237

    CAS  PubMed  Google Scholar 

  6. Deichmann M, Kronenwett R, Haas R . Expression of the human immunodeficiency virus type-1 coreceptors CXCR-4 (fusin, LESTR) and CKR-5 in CD34+ hematopoietic progenitor cells Blood 1997 89: 3522–3528

    CAS  PubMed  Google Scholar 

  7. Möhle R, Bautz F, Rafii S, Moore MAS, Brugger W, Kanz L . The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor-1 Blood 1998 91: 4523–4530

    PubMed  Google Scholar 

  8. Voermans C, Gerritsen WR, von dem Borne AEG Kr, van der Schoot CE . Increased migration of cord blood-derived CD34+ cells, as compared to bone marrow and mobilized peripheral blood CD34+ cells across uncoated or fibronectin-coated filters Exp Hem 1999 27: 1806–1814

    Article  CAS  Google Scholar 

  9. Kim CH, Broxmeyer HE . In vitro behavior of hematopoietic progenitor cells under the influence of chemoattractants: stromal cell-derived factor-1, steel factor, and the bone marrow environment Blood 1998 91: 100–110

    CAS  PubMed  Google Scholar 

  10. Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa S, Kitamura Y, Yoshida N, Kikutani H, Kishimoto T . Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1 Nature 1996 382: 635–638

    Article  CAS  PubMed  Google Scholar 

  11. Ma Q, Jones D, Borghesani PR, Segal RA, Nagasawa T, Kishimoto T, Bronson RT, Springer TA . Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR-4- and SDF-1-deficient mice Proc Natl Acad Sci USA 1998 95: 9448–9453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zou Y-R, Kottmann AH, Kudora M, Taniuchi I, Littman DR . Function of the chemokine receptor CXCR-4 in haematopoiesis and in cerebellar development Nature 1998 393: 595–599

    Article  CAS  PubMed  Google Scholar 

  13. 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 CXCR-4 Science 1999 283: 845–848

    Article  CAS  PubMed  Google Scholar 

  14. Voermans C, Kooi MLK, Rodenhuis S, van der Lelie J, van der Schoot CE, Gerritsen WR . In vitro migratory capacity of CD34+ cells is related to hematopoietic recovery after autologous stem cell transplantation Blood 2001 97: 799–804

    Article  CAS  PubMed  Google Scholar 

  15. Möhle R, Failenschmid C, Bautz F, Kanz L . Overexpression of the chemokine receptor CXCR4 in B cells chronic lymphocytic leukemia is associated with increased functional response to stromal cell-derived factor-1 (SDF-1) Leukemia 1999 13: 1954–1959

    Article  PubMed  Google Scholar 

  16. Dürig J, Rosenthal C, Elmaagacli A, Heyworth C, Halfmeyer K, Kasper C, Novotny J, Dührsen U . Biological effects of stromal-derived factor-1α on normal and CML CD34+ haemopoietic cells Leukemia 2000 14: 1652–1660

    Article  PubMed  Google Scholar 

  17. Bradstock KF, Makrynikola V, Bianci A, Shen W, Hewson J, Gottlieb DJ . Effects of the chemokine stromal cell-derived factor-1 on the migration and localization of precursor-B acute lymphoblastic leukemia cells within bone marrow stromal layers Leukemia 2000 14: 882–888

    Article  CAS  PubMed  Google Scholar 

  18. Löwenberg B, Downing JR, Burnett A . Acute myeloid leukemia N Engl J Med 1999 341: 1051–1062

    Article  PubMed  Google Scholar 

  19. Kluin-Nelemans J, Van Wering E, Van Der Schoot C, Adriaansen H, Van'T Veer M, Van Dongen J, Gratama J Dutch Co-operative Study Group on Immunophenotyping of Haematological Malignancies (SIHON). SIHONSCORE: a scoring system for external quality control of leukaemia/lymphoma immunophenotyping measuring all analytical phases of laboratory performance Br J Haematol 2001 112: 337–343

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  21. Dedhar S . Integrins and signal transduction Curr Opin Hematol 1999 6: 37–43

    Article  CAS  PubMed  Google Scholar 

  22. Clark EA, Brugge JS . Integrins and signal transduction pathways: the road taken Science 1995 268: 233–239

    Article  CAS  PubMed  Google Scholar 

  23. Liesveld JL, Dispersio JF, Abboud CN . Integrins and adhesive receptors in normal and leukemic CD34+ progenitor cells: potential regulatory checkpoints for cellular traffic Leuk Lymphoma 1994 14: 19–28

    Article  CAS  PubMed  Google Scholar 

  24. Bendall LJ, Kortlepel K, Gottlieb DJ . Human acute myeloid leukemia cells bind to bone marrow stroma via a combination of beta-1 and beta-2 integrin mechanisms Blood 1993 82: 3125–3132

    CAS  PubMed  Google Scholar 

  25. Weimar IS, Voermans C, Bourhis J-H, Miranda N, van den Berk PCM, Nakamura T, de Gast GC, Gerritsen WR . Hepatocyte growth factor/scatter factor (HGF/SF) affects proliferation and migration of myeloid leukemic cells Leukemia 1998 12: 1195–1203

    Article  CAS  PubMed  Google Scholar 

  26. Pelletier AJ, van Der Laan LJ, Hildbrand P, Siani MA, Thompson DA, Dawson PE, Torbett BE, Salomon DR . Presentation of chemokine SDF-1α by fibronectin mediates directed migration of T cells Blood 2000 96: 2682–2690

    CAS  PubMed  Google Scholar 

  27. Möhle R, Schittenhelm M, Failenschmid C, Bautz F, Kratz-Albers K, Serve H, Brugger W, Kanz L . Functional response of leukemic blasts to stromal cell-derived factor-1 correlates with preferential expression of the chemokine receptor CXCR-4 in acute myelomonocytic and lymphoblastic leukemia Br J Haematol 2000 110: 563–572

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are grateful to Colette van den Bogaard from the HIT lab and all hematologists and specialists for internal diseases from the Netherlands Cancer Institute, Amsterdam for collecting bone marrow and peripheral blood samples of AML patients. We also thank Dr van ‘t Veer of the Hovon Review Committee for MDS and AML. Furthermore, we acknowledge the specialists for internal diseases of the Free University, Onze Lieve Vrouwe Gasthuis and Slotervaart Hospital Amsterdam, Spittaal Hospital Zutphen, Lucas Hospital Apeldoorn, RKZ Heemskerk, Zeeweg Hospital IJmuiden, Gelderse Vallei Bennekom, SFG Rotterdam, Bronovo Hospital Den Haag, Mesos Medical Center, Utrecht and the Rijnstate Hospital Arnhem, for their cooperation with this project. We thank Dr Dirk Roos for critically reading the manuscript.

Author information

Authors and Affiliations

  1. Division of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands

    C Voermans

  2. Department of Experimental Immunohematology, CLB and Laboratory for Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

    C Voermans, WPM van Heese, I de Jong & CE van der Schoot

  3. Division of Gene Therapy Program, Department of Medical Oncology, University Hospital of Vrije Universiteit, Amsterdam, The Netherlands

    WR Gerritsen

  4. Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands

    CE van der Schoot

Authors
  1. C Voermans
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. WPM van Heese
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I de Jong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. WR Gerritsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. CE van der Schoot
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Voermans, C., van Heese, W., de Jong, I. et al. Migratory behavior of leukemic cells from acute myeloid leukemia patients. Leukemia 16, 650–657 (2002). https://doi.org/10.1038/sj.leu.2402431

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2402431

Keywords

This article is cited by

Search

Advanced search

Quick links