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Role of the microenvironment in promoting angiogenesis in acute myeloid leukemia
Author(s) -
Litwin Craig,
Leong Kevin G.,
Zapf Richard,
Sutherland Heather,
Naiman Sheldon C.,
Karsan Aly
Publication year - 2002
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.10092
Subject(s) - angiogenesis , bone marrow , endostatin , vascular endothelial growth factor , neovascularization , pathology , myeloid , in vivo , cd34 , cancer research , biology , medicine , stem cell , microbiology and biotechnology , vegf receptors
Angiogenesis is a crucial event in the survival and progression of solid tumors. To determine whether angiogenesis in acute myeloid leukemia (AML) is an intrinsic property of leukemic cells, the vascularity of bone marrow biopsies was determined. Bone marrow vascularity in newly diagnosed or post‐chemotherapy AML patients was increased 4‐fold ( P < 0.01) and 8.7‐fold ( P < 0.01), respectively, relative to controls. Vascular endothelial growth factor (VEGF) expression by AML blast cells was assessed by immunohistochemistry, and bone marrow cell supernatants were assayed for secretion of VEGF, fibroblast growth factor‐2 (FGF‐2), and endostatin by enzyme‐linked immunosorbent assay. Diffuse cytoplasmic and strong extracellular VEGF immunoreactivity was seen in bone marrow aspirates from AML patients, but not controls. In contrast, there was no difference in the levels of VEGF, FGF‐2, and endostatin secreted by mononuclear cells cultured from bone marrows of AML patients compared to normal controls following two days of culture in vitro. Total angiogenic potential of bone marrow cell supernatants was assessed by endothelial sprouting in vitro and by a chick chorioallantoic membrane assay. No differences were found between 2‐day conditioned medium from normal and AML bone marrow mononuclear cells in either assay. Our data show a discrepancy between bone marrow vascularity and VEGF expression in vivo and VEGF expression and angiogenesis from 2‐day conditioned medium ex vivo. This suggests that angiogenesis in AML likely represents a response to microenvironmental factors in vivo, rather than being an intrinsic property of leukemic cells. Am. J. Hematol. 70:22–30, 2002. © 2002 Wiley‐Liss, Inc.