Primary human acute myeloid leukaemia cells increase the proliferation of microvascular endothelial cells through the release of soluble mediators

• Published in: British journal of haematology 2009-01, Vol.144 (1), p.53-68
• Main Authors: Hatfield, Kimberley, Øyan, Anne M., Ersvaer, Elisabeth, Kalland, Karl‐Henning, Lassalle, Philippe, Gjertsen, Bjørn T., Bruserud, Øystein
• Format: Article
• Language: English
• Subjects: acute myeloid leukaemia; Adult; Aged; Aged, 80 and over; angiopoietin; Angiopoietin-1 - metabolism; Base Sequence; Biological and medical sciences; Cell Proliferation; Chemokine CXCL10 - genetics; Chemokine CXCL11 - genetics; Chemokine CXCL9 - genetics; Coculture Techniques; endocan; endothelial cells; Endothelial Cells - metabolism; Endothelial Cells - pathology; Female; Gene Expression Profiling; Hematologic and hematopoietic diseases; Humans; Interleukin-8 - genetics; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lung - blood supply; Male; Medical sciences; Microcirculation; Middle Aged; Molecular Sequence Data; Neovascularization, Pathologic; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction - methods; signal transducers and activators of transcription; Signal Transduction - physiology; STAT Transcription Factors - genetics; STAT Transcription Factors - metabolism; Up-Regulation
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2008.07411.x

Summary 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.