Expression of angiopoietin-1 and its receptor TEK in hematopoietic cells from patients with myeloid leukemia.
Apart from endothelial cells, the receptor tyrosine kinase TEK/Tie-2 is also expressed by primitive hematopoietic stem cells. While the role of this receptor and its ligand angiopoietin-1 (ang-1) during angiogenesis has been intensively studied before, little is known about their function in normal or malignant hematopoiesis. Recently several studies suggested that TEK plays an important role in the proliferation of primitive hematopoietic cells. We, therefore, analyzed blood cells of healthy donors and leukemia patients for expression of TEK and ang-1 by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and Northern blotting. We found an increased expression of the receptor and its ligand in 11 of 17 cases of acute and chronic myeloid leukemia (CML) but not in four lymphocytic leukemias or five myeloid leukemias in remission. Abundant ang-1 message could also be detected in 4/6 myeloid and 1/9 cell lines of lymphocytic origin, but only one cell line co-expressed the TEK receptor, suggesting that ang-1 and TEK were probably expressed by different subsets of cells in the leukemic samples. Recently, several studies have indicated that angiogenic factors like ang-1 and vascular endothelial growth factor can enhance the proliferation of normal and malignant hematopoietic cells. The expression of both the TEK receptor and its ligand in acute myeloid leukemia (AML) and CML patients might, therefore, suggest an involvement of these genes in the pathogenesis of myeloproliferative disorders.
Müller
Anke
A
Institut für Pathologie, Universitätsklinikum Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany.
Lange
Karin
K
Gaiser
Timo
T
Hofmann
Manfred
M
Bartels
Heinrich
H
Feller
Alfred C
AC
Merz
Hartmut
H
D000208:Acute Disease; D042683:Angiopoietin-1; D002908:Chronic Disease; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D042787:Receptor, TIE-2; D020133:Reverse Transcriptase Polymerase Chain Reaction
D042683:Angiopoietin-1; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2