EXPRESSION OF TIE RECEPTOR TYROSINE KINASE IN HUMAN LEUKEMIA-CELL LINES

The tie gene encodes a receptor tyrosine kinase that together with its thus far unidentified ligand appears to play a distinct role in the r egulatory pathway of early hematopoiesis and angiogenesis. Here, we at tempted to define the possible involvement of tie in the pathobiology of hematopoietic malignancies by examining tie mRNA expression in huma n leukemia and lymphoma cells. We used a large panel of 93 well-charac terized human continuous leukemia-lymphoma cell lines as model systems for the various hematopoietic cell lineages. At the Northern blot lev el, none of the 27 lymphoid leukemia or lymphoma-derived cell lines (o riginating from four B-precursor leukemia, four B-cell leukemia, four B-cell non-Hodgkin's lymphoma, two myeloma, two Burkitt lymphoma, four T-cell leukemia, five Hodgkin lymphoma, two anaplastic large cell lym phoma) tested expressed tie transcripts, whereas 23/ 42 (55%) of the m yeloid cell lines analyzed expressed tie mRNA: in detail, 15 of 20 (75 %) megakaryocytic, five of 11 (45%) erythroid, three of seven (43%) my elocytic and none of four monocytic cell lines were tie mRNA positive. In the reverse transcriptase-polymerase chain reaction analysis, whic h can detect very low levels of mRNA expression, all 12 myeloid cell l ines and 19 of 39 (48%) lymphoid cell lines were positive. In experime nts aimed at inducing cellular differentiation over an incubation peri od of 4 days, the phorbol ester PMA strongly enhanced tie mRNA express ion in one erythroid and in one myelocytic cell line, but (like thromb opoietin) down-regulated tie mRNA expression in two megakaryocytic cel l lines. Taken together these results indicate that tie is predominant ly expressed in leukemia cells derived from the myeloid cell lineages (and here in particular in megakaryoblastic cells) and not in lymphoid leukemia cells. These observations provide some evidence for the hypo thesis that tie is a receptor for a regulatory factor involved in norm al and plausibly also leukemic hematopoiesis. (C) 1997 Elsevier Scienc e Ltd.