title: Soluble mediators released by acute myeloid leukemia cells increase capillary-like networks.
abstract: Increased bone marrow angiogenesis is seen in several hematological malignancies, including acute myeloid leukemia (AML). We used a co-culture assay of endothelial and vascular smooth muscle cells (vSMC) to investigate the effects of AML-conditioned medium on capillary networks. We investigated primary AML cells derived from 44 unselected patients and observed that for a large subset of patients, the constitutive cytokine release by the leukemic cells stimulated endothelial cell organization into capillary-like networks, while there were only minor or no effects for other patients. We analyzed the constitutive AML cell release of 31 cytokines for all the patients and performed a hierarchical cluster analysis of the cytokine profile which identified two major patient subsets that differed in their ability to enhance capillary-like networks; increased capillary-like networks was then associated with high constitutive release of several cytokines and especially high levels of several pro-angiogenic chemokines. Significantly increased network formation was not seen for any of the 11 acute lymphoblastic leukemia patients investigated. The cytokine response by activated normal T cells inhibited endothelial network formation in our in vitro model of angiogenesis and activated normal monocytes had only a minor influence on tube formation. Our study shows that AML-derived cytokines can induce the organization of endothelial cells into vessel-like structures.
authors.affiliation: Section for Hematology, Department of Medicine, Haukeland University Hospital, and Department of Hematology, University of Bergen, Bergen, Norway. mmakh@med.uib.no
authors.forename: Kimberley J
authors.initials: KJ
authors.lastname: Hatfield
authors.forename: Lasse
authors.initials: L
authors.lastname: Evensen
authors.forename: Håkon
authors.initials: H
authors.lastname: Reikvam
authors.forename: James B
authors.initials: JB
authors.lastname: Lorens
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Bruserud
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002196:Capillaries / Q000473:pathology*; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D009389:Neovascularization, Pathologic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines