Analysis of Tie receptor tyrosine kinase in haemopoietic progenitor and leukaemia cells

Authors

  • Eola Kukk,

    1. Molecular/Cancer Biology Laboratory, Transplantation Laboratory, Haartman Institute, University of Helsinki, and Departments of Clinical Chemistry and Internal Medicine, Division of Clinical Haematology, Helsinki University Central Hospital, Finland,
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  • Ulla Wartiovaara,

    1. Molecular/Cancer Biology Laboratory, Transplantation Laboratory, Haartman Institute, University of Helsinki, and Departments of Clinical Chemistry and Internal Medicine, Division of Clinical Haematology, Helsinki University Central Hospital, Finland,
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  • Yuji Gunji,

    1. Molecular/Cancer Biology Laboratory, Transplantation Laboratory, Haartman Institute, University of Helsinki, and Departments of Clinical Chemistry and Internal Medicine, Division of Clinical Haematology, Helsinki University Central Hospital, Finland,
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  • Jaakko Kaukonen,

    1. Molecular/Cancer Biology Laboratory, Transplantation Laboratory, Haartman Institute, University of Helsinki, and Departments of Clinical Chemistry and Internal Medicine, Division of Clinical Haematology, Helsinki University Central Hospital, Finland,
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  • Hans-Jörg Bühring,

    1. Medizinische Universitätsklinik, Abteilung II, Tübingen, Germany,
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  • Irene Rappold,

    1. Medizinische Universitätsklinik, Abteilung II, Tübingen, Germany,
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  • Marja-Terttu Matikainen,

    1. Centre for Biotechnology, University of Turku, Turku, Finland,
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  • Pirkko Vihko,

    1. Department of Clinical Chemistry, Oulu University, Oulu, Finland
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  • Juha Partanen,

    1. Molecular/Cancer Biology Laboratory, Transplantation Laboratory, Haartman Institute, University of Helsinki, and Departments of Clinical Chemistry and Internal Medicine, Division of Clinical Haematology, Helsinki University Central Hospital, Finland,
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  • Aarno Palotie,

    1. Molecular/Cancer Biology Laboratory, Transplantation Laboratory, Haartman Institute, University of Helsinki, and Departments of Clinical Chemistry and Internal Medicine, Division of Clinical Haematology, Helsinki University Central Hospital, Finland,
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  • Kari Alitalo,

    1. Molecular/Cancer Biology Laboratory, Transplantation Laboratory, Haartman Institute, University of Helsinki, and Departments of Clinical Chemistry and Internal Medicine, Division of Clinical Haematology, Helsinki University Central Hospital, Finland,
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  • Riitta Alitalo

    1. Molecular/Cancer Biology Laboratory, Transplantation Laboratory, Haartman Institute, University of Helsinki, and Departments of Clinical Chemistry and Internal Medicine, Division of Clinical Haematology, Helsinki University Central Hospital, Finland,
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Dr Eola Kukk Molecular Cancer Biology Laboratory, PL21, 0014 University of Helsinki, Helsinki, Finland

Abstract

We generated a panel of monoclonal antibodies against the extracellular domain of the Tie receptor tyrosine kinase and studied its expression in human haemopoietic and tumour cell lines and in samples from leukaemia patients. Most of the erythroblastic/megakaryoblastic (6/8), 2/7 myeloid and 3/6 B-lymphoblastic leukaemia cell lines were Tie-positive. The erythroblastic/megakaryoblastic leukaemia cell lines also expressed the related Tie-2/Tek gene and, surprisingly, its recently cloned ligand gene angiopoietin-1, which was located in chromosome 8q23.1. In addition, 16% of freshly isolated leukaemia samples were Tie positive. Peripheral blood mononuclear cells were Tie negative, but a few Tie positive cells were found in immunoperoxidase staining of mobilized peripheral blood stem cells. Long-term culture of isolated umbilical cord blood CD34+Tie+ and CD34+Tiecells indicated that the Tie+ fraction contained a slightly higher frequency of cobblestone area forming cells (CAFC). Thus, Tie is expressed on haemopoietic progenitor cells and some leukaemic blasts. The coexpression of Tie-2 and angiopoietin-1 in megakaryoblastic leukaemia cell lines suggests the existence of an autocrine ligand/receptor signalling loop in these cells.

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