title: Phenotypic, genotypic, and functional characterization of normal and acute myeloid leukemia-derived marrow endothelial cells.
abstract: In addition to participation in homing, egress, and transmigration of hematopoietic cells, marrow endothelium also contributes to cell proliferation and survival. Endothelial cells from multiple vascular beds are able to prevent spontaneous or therapy-induced apoptosis in acute myelogenous leukemia (AML) blasts. Marrow-derived endothelial cells from leukemia patients have not been well-characterized, and in this work, endothelial cells were purified from marrow aspirates from normal subjects or from newly diagnosed AML patients to compare these cells phenotypically and functionally. By reverse transcription polymerase chain reaction, these cells express CD31, Tie-2, vascular endothelial growth factor (VEGF), and endothelial nitric oxide synthase (eNOS), supporting endothelial origin. They take up acetyl low-density lipoprotein and are able to form tubular structures. Culture of AML cells with endothelial cells from both normal and AML subjects supported adhesion, transmigration, and leukemia colony-forming unit outgrowth. RNA-sequencing analysis revealed 130 genes significantly up- or downregulated in AML-derived endothelial cells as compared with those derived from normal marrow. The genes differentially expressed (p < 0.001) were included in biological function categories involving cancer, cell development, cell growth and proliferation, cell signaling, inflammatory response, and cell death and survival. Further pathway analysis revealed upregulation of c-Fos and genes involved in chemotaxis such as CXCL16. AML-derived endothelial cells are similar in phenotype and function to their normal marrow-derived counterparts, but genomic analysis suggests a differential signature with altered expression of genes, which could play a role in leukemogenesis or leukemia cell maintenance in the marrow microenvironment.
authors: Department of Medicine, Hematology/Oncology, James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY.
authors: Russell J
authors: RJ
authors: Pizzo
authors: Department of Medicine, Hematology/Oncology, James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY.
authors: Mitra
authors: M
authors: Azadniv
authors: Department of Medicine, Hematology/Oncology, James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY.
authors: Naxin
authors: N
authors: Guo
authors: Department of Medicine, Hematology/Oncology, James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY.
authors: Joshua
authors: J
authors: Acklin
authors: Department of Medicine, Hematology/Oncology, James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY.
authors: Kimberly
authors: K
authors: Lacagnina
authors: Department of Pathology and Laboratory Medicine, James P. Wilmot Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, NY.
authors: Myra
authors: M
authors: Coppage
authors: Department of Medicine, Hematology/Oncology, James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY. Electronic address: Jane_Liesveld@urmc.rochester.edu.
authors: Jane L
authors: JL
authors: Liesveld
mesh_terms: D015703:Antigens, CD / Q000235:genetics; D001854:Bone Marrow Cells / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D019070:Cell Lineage / Q000235:genetics; D000071063:Endoglin; D042783:Endothelial Cells / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods*; D005838:Genotype; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics; D042787:Receptor, TIE-2 / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D020298:U937 Cells; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A; D052250:Nitric Oxide Synthase Type III; D042787:Receptor, TIE-2