Cancer Immunology, Immunotherapy

, Volume 55, Issue 7, pp 830–840 | Cite as

T lymphocyte chemotactic chemokines in acute myelogenous leukemia (AML): local release by native human AML blasts and systemic levels of CXCL10 (IP-10), CCL5 (RANTES) and CCL17 (TARC)

  • Astrid Marta Olsnes
  • Dmitri Motorin
  • Anita Ryningen
  • Andrey Y. Zaritskey
  • Øystein BruserudEmail author
Original Article


T cell targeting immunotherapy is now considered in acute myelogenous leukemia (AML), and local recruitment of antileukemic T cells to the AML microcompartment will then be essential. This process is probably influenced by both intravascular as well as extravascular levels of T cell chemotactic chemokines. We observed that native human AML cells usually showed constitutive secretion of the chemotactic chemokines CXCL10 and CCL5, whereas CCL17 was only released for a subset of patients and at relatively low levels. Coculture of AML cells with nonleukemic stromal cells (i.e., fibroblasts, osteoblasts) increased CXCL10 and CCL17 levels whereas CCL5 levels were not altered. However, a wide variation between patients in both CXCL10 and CCL5 levels persisted even in the presence of the stromal cells. Neutralization of CXCL10 and CCL5 inhibited T cell migration in the presence of native human AML cells. Furthermore, serum CCL17 and CXCL10 levels varied between AML patients and were determined by disease status (both chemokines) as well as patient age, chemotherapy and complicating infections (only CCL17). Thus, extravascular as well as intravascular levels of T cell chemotactic chemokines show a considerable variation between patients that may be important for T cell recruitment and the effects of antileukemic T cell reactivity in local AML compartments.


Acute myelogenous leukemia CXCL10 CCL5 CCL17 



The work was supported by the Norwegian Cancer Society and Olaf Ruunshaugens Foundation. The technical assistance of Line Wergeland and Kristin Paulsen is gratefully acknowledged.


  1. 1.
    Löwenberg B, Downing JR, Burnett A (1999) Acute myeloid leukemia. N Engl J Med 341:1051–1062CrossRefPubMedGoogle Scholar
  2. 2.
    Bruserud Ø (1999) Acute myelogenous leukemia blasts as accessory cells during T lymphocyte activation: possible implications for future therapeutic strategies. Leukemia 13:1175–1187CrossRefPubMedGoogle Scholar
  3. 3.
    Bruserud Ø, Gjertsen BT (2000) New strategies for the treatment of acute myelogenous leukemia: differentiation induction – present use and future possibilities. Stem Cells 18:157–165CrossRefPubMedGoogle Scholar
  4. 4.
    Bruserud Ø, Wendelbo Ø (2001) Biological treatment of acute myelogenous leukemia: how should T cell targeting immunotherapy be combined with intensive chemotherapy. Exp Opin Biol Ther 1:1005–1016CrossRefGoogle Scholar
  5. 5.
    Bruserud Ø, Ulvestad E (2000) Acute myelogenous leukemia blasts as accessory cells during in vitro T lymphocyte activation. Cell Immunol 206:35–50CrossRefGoogle Scholar
  6. 6.
    Luther SA, Cyster JG (2001) Chemokines as regulators of T cell differentiation. Nat Immunol 2:102–107CrossRefPubMedGoogle Scholar
  7. 7.
    Romagnani S (2001) Cytokines and chemoattractants in allergic inflammation. Mol Immunol 38:881–885CrossRefGoogle Scholar
  8. 8.
    Imai T, Nagira M, Takagi S et al (1999) Selective recruitment of CCR4-bearing Th2 cells toward antigen-presenting cells by the CC chemokines thymus and activation-regulated chemokine and macrophage-derived chemokine. Int Immunol 11:81–88CrossRefPubMedGoogle Scholar
  9. 9.
    Moser B, Wolf M, Walz A, Loetscher P (2004) Chemokines: multiple levels of leukocyte migration control. Trends Immunol 25:75–84CrossRefPubMedGoogle Scholar
  10. 10.
    Neville LF, Mathiak G, Bagasra Ø (1997) The Immunobiology of Interferon-gamma Inducible Protein 10 kD (IP-10): a novel, pleiotropic member of the C-X-C chemokine superfamily. Cytokine Growth F R 8:207–219CrossRefGoogle Scholar
  11. 11.
    Wendelbo Ø, Nesthus I, Sjo M, Paulsen K, Ernst P, Bruserud Ø (2004) Functional characterization of T lymphocytes derived from patients with acute myelogenous leukemia and chemotherapy-induced leukopenia. Cancer Immunol Immun 53:740–747Google Scholar
  12. 12.
    Bruserud Ø, Hovland R, Wergeland L, Huang T-s, Gjertsen BT (2003) Flt3-mediated signalling in human acute myelogenous leukemia (AML) blasts: a functional characterization of the effects of Flt3-ligand in AML cell populations with and without Flt3 abnormalities. Haematologica 88:416–428PubMedGoogle Scholar
  13. 13.
    Wheatley K, Burnett AK, Goldstone AH et al (1999) A simple, robust, validated and highly predictive index for the determination of risk-directed therapy in acute myeloid leukemia derived from the MRC AML 10 trial. Br J Haematol 107:69–79CrossRefPubMedGoogle Scholar
  14. 14.
    Bene MC, Castoldi G, Knapp W et al (1995) Proposals for the immunological classification of acute leukemias. Leukemia 9:1783–1786PubMedGoogle Scholar
  15. 15.
    Bruserud Ø, Ryningen A, Wergeland L, Glenjen NI, Gjertsen BT (2004) Osteoblasts increase proliferation and release of proangiogenic interleukin 8 by native human acute myelogenous leukemia blasts. Haematologica 89:391–402PubMedGoogle Scholar
  16. 16.
    Bruserud Ø, Gjertsen BT, Foss B, Huang T-s (2001) New strategies in the treatment of acute myelogenous leukemia (AML): in vitro culture of AML cells–the present use in experimental studies and the possible importance for future therapeutic strategies. Stem Cells 19:1–11CrossRefPubMedGoogle Scholar
  17. 17.
    Bruserud Ø, Tronstad KJ, Berge R (2005) In vitro culture of human osteosarcoma cell lines: a comparison of functional characteristics for cell lines cultured in medium without and with fetal calf serum. J Cancer Res Clin Oncol 741:24–34Google Scholar
  18. 18.
    Rochet N, Leroy P, Far DF, Ollier L, Loubat A, Rossi B (2003) CAL72: a human osteosarcoma cell line with unique effects on hematopoietic cells. Eur J Haematol 70:43–52CrossRefPubMedGoogle Scholar
  19. 19.
    Ryningen A, Wergeland L, Glenjen NI, Gjertsen BT, Bruserud Ø (2005) In vitro crosstalk between fibroblasts and native human acute myelogenous leukemia (AML) blasts via local cytokine networks results in increased proliferation and decreased apoptosis of AML cells as well as increased levels of proangiogenic Interleukin 8. Leukemia Res 292:185–196CrossRefGoogle Scholar
  20. 20.
    Bruserud Ø, Wendelbo Ø, Paulsen K (2004) Lipoteichoic acid derived from Enterococcus faecalis modulates the functional characteristics of both normal peripheral blood leukocytes and native human acute myelogenous leukemia blasts. Eur J Haematol 73:340–350CrossRefPubMedGoogle Scholar
  21. 21.
    Glenjen NI, Ersvær E, Ryningen A, Bruserud Ø (2004) In vitro effects of native human acute myelogenous leukemia blasts on fibroblasts and osteoblasts. Int J Cancer 111:858–867CrossRefPubMedGoogle Scholar
  22. 22.
    Øyan AM, Bo TH, Jonassen I et al (2005) CD34 expression in native human acute myelogenous leukemia blasts: Differences in CD34 membrane molecule expression are associated with different gene expression profiles. Cytometry B Clin Cytom 64:18–27CrossRefPubMedGoogle Scholar
  23. 23.
    Gjertsen BT, Øyan AM, Marzolf B et al (2002) Analysis of acute myelogenous leukemia: preparation of samples for genomic and proteomic analyses. J Hematother Stem Cell Res 11:469–481CrossRefPubMedGoogle Scholar
  24. 24.
    Bruserud Ø, Gjertsen BT, von Volkman HL (2000) In vitro culture of human acute myelogenous leukemia (AML) cells in serum-free media: studies of native AML blasts and AML cell lines. J Hematother Stem Cell Res 9:923–932CrossRefPubMedGoogle Scholar
  25. 25.
    Bruserud Ø, Glenjen NI (2005) Coculture of native human acute myelogenous leukemia blasts with fibroblasts and osteoblasts results in an increase of vascular endothelial growth factor levels. Eur J Haematol 74:24–34CrossRefPubMedGoogle Scholar
  26. 26.
    Gear AR, Camerini D (2003) Platelet chemokines and chemokine receptors: linking hemostasis, inflammation, and host defense. Microcirculation 10:335–350CrossRefPubMedGoogle Scholar
  27. 27.
    Panoskaltsis N, Reid CD, Knight SC (2003) Quantification and cytokine production of circulating lymphoid and myeloid cells in acute myelogenous leukaemia. Leukemia 17:716–730CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Astrid Marta Olsnes
    • 1
  • Dmitri Motorin
    • 2
    • 3
  • Anita Ryningen
    • 1
  • Andrey Y. Zaritskey
    • 2
  • Øystein Bruserud
    • 1
    Email author
  1. 1.Division for Hematology, Department of MedicineHaukeland University Hospital and The University of BergenBergenNorway
  2. 2.BMT Clinic and Faculty Therapy ChamberPavlov State Medical UniversitySt PetersburgRussia
  3. 3.Centre for Medical Studies, Moscow, Department Group for Laboratory MedicineThe National HospitalOsloNorway

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