title: Primary human acute myeloid leukaemia cells increase the proliferation of microvascular endothelial cells through the release of soluble mediators.
abstract: Bone marrow angiogenesis is suggested to play a role in the pathogenesis of acute myeloid leukaemia (AML) and endothelial cells may mediate chemosensitivity. This study investigated in vitro endothelial effects of coculture of microvascular endothelial cells (MVEC) with AML cells derived from 33 consecutive AML patients. A proliferation assay showed that (i) AML cells from the majority of patients examined increased endothelial cell proliferation, while cytokine neutralizing experiments had divergent effects on proliferation and (ii) the angiopoietin/Tie2 system was important for growth of AML cells, and angiopoietin-1 induced phosphorylation of signal transducers and activators of transcription (STAT) proteins in AML cells. Finally, gene expression profiling of MVEC cocultured with AML cells was conducted in non-contact cultures. Microarray analysis revealed that the majority of significantly expressed genes could be categorized into gene ontology terms involved in transcription, cellular organization and intracellular signalling. Our study indicates a role for the leukaemic-endothelium crosstalk in leukaemogenesis with enhancement of endothelial cell growth and increased AML cell proliferation possibly mediated by angiopoietin-1 and the STAT signalling pathway.
authors.affiliation: Section for Haematology, Institute of Medicine, University of Bergen, Norway.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Hatfield
authors.forename: Anne M
authors.initials: AM
authors.lastname: Øyan
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ersvaer
authors.forename: Karl-Henning
authors.initials: KH
authors.lastname: Kalland
authors.forename: Philippe
authors.initials: P
authors.lastname: Lassalle
authors.forename: Bjørn T
authors.initials: BT
authors.lastname: Gjertsen
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Bruserud
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D042683:Angiopoietin-1 / Q000378:metabolism*; D001483:Base Sequence; D049109:Cell Proliferation; D054357:Chemokine CXCL10 / Q000235:genetics; D054371:Chemokine CXCL11 / Q000235:genetics; D054370:Chemokine CXCL9 / Q000235:genetics; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D008168:Lung / Q000098:blood supply; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D042683:Angiopoietin-1; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D016209:Interleukin-8; D050791:STAT Transcription Factors