ANALYSIS OF TIE RECEPTOR TYROSINE KINASE IN HEMATOPOIETIC PROGENITOR AND LEUKEMIA-CELLS

We generated a panel of monoclonal antibodies against the extracellula r domain of the Tie receptor tyrosine kinase and studied its expressio n in human haemopoietic and tumour cell lines and in samples from leuk aemia patients, Most of the erythroblastic/megakaryoblastic (6/8), 2/7 myeloid and 3/6 B-lymphoblastic leukaemia cell lines were Tie-positiv e, The erythroblastic/megakaryoblastic leukaemia cell lines also expre ssed the related Tie-2/Tek gene and, surprisingly, its recently cloned ligand gene angiopoietin-1, which was located in chromosome 8q23.1. I n addition, 16% of freshly isolated leukaemia samples were Tie positiv e. Peripheral blood mononuclear cells were Tie negative, but a few Tie positive cells were found in immunoperoxidase staining of mobilized p eripheral blood stem cells. Long-term culture of isolated umbilical co rd blood CD34(+)Tie(+) and CD34(+)Tie(-)cells indicated that the Tie() fraction contained a slightly higher frequency of cobblestone area f orming cells (CAFC). Thus, Tie is expressed on haemopoietic progenitor cells and some leukaemic blasts. The coexpression of Tie-2 and angiop oietin-1 in megakaryoblastic leukaemia cell lines suggests the existen ce of an autocrine ligand/receptor signalling loop in these cells.