Evidence of increased angiogenesis in patients with acute myeloid leukemia.
Angiogenesis plays a key role in solid tumor growth. The purpose of this work was to study angiogenesis in acute myeloid leukemia (AML). We stained bone marrow samples from 20 adult patients with untreated AML and 20 normal controls using endothelial cell markers (ULEX-E and von Willebrand factor [vWF]). The number of vessels per millimeter length of bone marrow core biopsy specimen was scored by light microscopy. Using ULEX-E staining, AML marrows had (average +/- SEM) 8.3 +/- 3.6 vessels/mm (range, 3.7-19.3), whereas normal marrows had 4.3 +/- 1.8 vessels/mm (range, 1.6-7.9). A similar difference was noted using vWF staining (8.6 +/- 3.0 vessels/mm vs 4. 9 +/- 2.2 vessels/mm in AML vs normal bone marrows, respectively). The differences between the numbers of vessels/mm in AML and normal marrows were highly significant (P <.0001 for both ULEX-E and vWF staining). When analyzed by FAB category, there was no difference in the average number of vessels/mm among the different subgroups of AML. Using reverse transcriptase polymerase chain reaction, we observed that the HL-60 and U937 human AML cell lines and 4 of 4 freshly isolated AML cells from untreated patients expressed mRNA for vascular endothelial growth factor (VEGF). Both cell lines as well as all fresh AML isolates tested expressed VEGF protein. Basic fibroblast growth factor was expressed only in HL-60 cells and in only 3 of 4 fresh AML samples. These observations suggest that angiogenesis may play a role in the pathogenesis of AML. Inhibition of angiogenesis could constitute a novel strategy for the treatment of AML. (Blood. 2000;95:309-313).
Hussong
J W
JW
Department of Pathology, ARUP Laboratories, Salt Lake City, UT, USA.
Rodgers
G M
GM
Shami
P J
PJ
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001853:Bone Marrow / Q000098:blood supply* / Q000473:pathology*; D001854:Bone Marrow Cells / Q000166:cytology*; D016228:Endothelial Growth Factors / Q000032:analysis / Q000235:genetics*; D004730:Endothelium, Vascular / Q000166:cytology / Q000473:pathology; D018922:HL-60 Cells; D006801:Humans; D007150:Immunohistochemistry; D037102:Lectins; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D008222:Lymphokines / Q000032:analysis / Q000235:genetics*; D009389:Neovascularization, Pathologic; D037121:Plant Lectins; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020298:U937 Cells; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D016228:Endothelial Growth Factors; D037102:Lectins; D008222:Lymphokines; D037121:Plant Lectins; C036850:Ulex europaeus lectins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014841:von Willebrand Factor