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Soluble mediators released by acute myeloid leukemia cells increase capillary‐like networks

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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.
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Document Type: Research Article

Publication date: December 1, 2012

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