title: Expression of endothelial cell-associated molecules in AML cells.
abstract: Recently, it has been clarified that interaction between hematopoietic cells and endothelial cells is important in normal hematopoiesis and leukemogenesis. In this study, we examined the relationship between AML cells and endothelial cells by analyzing the expression profile of angiogenic factors, angiopoietin-1 (Ang-1), Ang-2, Tie-2 (a receptor for angiopoietins) and vascular endothelial growth factor (VEGF). Our results demonstrated that CD7(+)AML expressed Ang-2 mRNA frequently and integrin-family adhesion molecules (CD11c and CD18) intensively, suggesting the close correlation with endothelial cells. On the other hand, in t(8;21) AML cells, expression of Ang-2 was infrequent and expression of integrin-family adhesion molecules (CD11b, CD11c and CD18) was weak, suggesting the sparse association with endothelial cells. As for CD7(+)AML cells, despite the frequent and intense expression of endothelial cell-associated molecules (such as Ang-2, CD11c and CD18), intensity of Tie-2 expression was quite low (P < 0.05). Ang-2 expressed in CD7(+)AML cells is not considered to act in an autocrine fashion, but to work on endothelial cells to "feed" leukemic cells. Although Ang-2 is recognized as a natural antagonist for Tie-2, our data presented here suggested the alternative role of Ang-2 in the relationship between endothelial cells and leukemia cells, at least in a subset of leukemia such as CD7(+)AML. These results were supported by the study using AML cell lines, KG-1 (CD7 negative) and its subline KG-1a (CD7 positive); KG-1 had mRNA expression profile of Ang-1(+)Ang-2(-)Tie-2(+), while KG-1a showed Ang-1(+)Ang-2(+)Tie-2(-). These difference in the expression profile of angiogenic factors between CD7(+)AML and t(8;21)AML may explain the characteristic morphological features of these leukemias (CD7(+)AML as blastic type and t(8;21)AML as differentiative type).
authors.affiliation: Department of Internal Medicine, Division of Hematology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Watarai
authors.forename: H
authors.initials: H
authors.lastname: Miwa
authors.forename: M
authors.initials: M
authors.lastname: Shikami
authors.forename: K
authors.initials: K
authors.lastname: Sugamura
authors.forename: M
authors.initials: M
authors.lastname: Wakabayashi
authors.forename: A
authors.initials: A
authors.lastname: Satoh
authors.forename: K
authors.initials: K
authors.lastname: Tsuboi
authors.forename: A
authors.initials: A
authors.lastname: Imamura
authors.forename: H
authors.initials: H
authors.lastname: Mihara
authors.forename: Y
authors.initials: Y
authors.lastname: Katoh
authors.forename: K
authors.initials: K
authors.lastname: Kita
authors.forename: M
authors.initials: M
authors.lastname: Nitta
mesh_terms: D000208:Acute Disease; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D019011:Antigens, CD7 / Q000032:analysis; D001773:Blood Cells / Q000473:pathology; D001854:Bone Marrow Cells / Q000473:pathology; D018821:CD18 Antigens / Q000096:biosynthesis / Q000235:genetics; D002453:Cell Cycle; D002478:Cells, Cultured / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D016130:Immunophenotyping; D016167:Integrin alphaXbeta2 / Q000096:biosynthesis / Q000235:genetics; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008222:Lymphokines / Q000096:biosynthesis* / Q000235:genetics; D016177:Macrophage-1 Antigen / Q000096:biosynthesis / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics*; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins; D042787:Receptor, TIE-2; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D019011:Antigens, CD7; D018821:CD18 Antigens; D016228:Endothelial Growth Factors; D016167:Integrin alphaXbeta2; D008222:Lymphokines; C105373:MEN1 protein, human; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D042787:Receptor, TIE-2