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Microvascular endothelial cells increase proliferation and inhibit apoptosis of native human acute myelogenous leukemia blasts
Author(s) -
Hatfield Kimberley,
Ryningen Anita,
Corbascio Matthias,
Bruserud Øystein
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22180
Subject(s) - cytokine , leukemia , cancer research , clonogenic assay , endothelial stem cell , paracrine signalling , haematopoiesis , immunology , biology , cell growth , apoptosis , stem cell , microbiology and biotechnology , in vitro , biochemistry , receptor
Abstract Interactions between acute myelogenous leukemia (AML) blasts and neighbouring endothelial cells in the bone marrow seem important both for disease development and susceptibility to chemotherapy. We investigated the effects of soluble mediators released by microvascular endothelial cells on native human AML cells. AML cells derived from 33 patients were cocultured with microvascular endothelial cells, separated by a semipermeable membrane. We investigated the effect of coculture on AML cell proliferation, viability/apoptosis and cytokine release. Coculture increased AML cell proliferation, and this growth enhancement included the clonogenic leukemia cell subset. Increased release of several soluble mediators was also detected (interleukin 3, interleukin 6, granulocyte‐macrophage and granulocyte colony‐stimulating factors) in cocultures. Our cytokine neutralization experiments suggest that an intercellular crosstalk involving several soluble mediators contribute to the increased leukemia cell proliferation. The presence of endothelial cells had an additional antiapoptotic effect on the AML cells. The endothelial cells did not have any growth‐enhancing effect on native human acute lymphoblastic leukemia cells. Our in vitro results suggest that the release of soluble mediators by microvascular endothelial cells supports leukemic hematopoiesis through paracrine mechanisms by direct enhancement of AML blast proliferation and by inhibition of leukemic cell apoptosis. © 2006 Wiley‐Liss, Inc.