Abstract
Angiogenesis plays a key role in the growth of solid tumors and in the development of metastases. An increased angiogenesis in bone marrow has been reported in children with acute lymphoblastic leukemia (Am J Pathol 150:815-821,1997). The purpose of the present study was to assess angiogenesis in bone marrow biopsies from 47 patients with newly diagnosed, untreated acute myeloid leukemia (AML). Control specimens (n=20) were obtained from patients with neo-plasic disorders without bone marrow involvement. The FAB distribution of the AML cases was as follows: 7 M1, 21 M2,1 M3,7 M4, 7 M5,2 M6 and 2 AMLs without defined subtype. The endothelial cells of microvessels were highlighted by immunohistochemical staining for thrombomodulin (TM) and von Willebrand factor (vWF). The 3 areas with the highest microvessel density in representative sections of each bone marrow core biopsy specimen were selected and the microvessels scored in x500 fields by two observers using light microscopy. A significant correlation was found between microvessel counts in bone marrow sections stained by vWF and TM antibodies (r = 0.828; p< 0.001). Using TM staining, AML marrows had (median [interquartile range]) 25.5 [22.1-29.3] microvessels / field while normal marrows had 13.2 [11.4-14.8] microvessels / field. Using vWF staining of the same specimens, AML marrows had 22.9 [16.1-26.2] microvessels / field while normal marrows had 9.8 [7.7-10.5] microvessels / field. The differences between the number of vessels / field in AML and controls were statistically significant for both TM (p= 0.0003) and vWF (p= 0.001) staining. When analyzed by FAB category, there was no difference in the average number of microvessels / field between the different subgroups of AML. In summary, we demonstrated that bone marrow in AML is associated with increased microvessel density. These findings suggest that antiangiogenic therapy might constitute a novel strategy for the treatment of acute myeloid leukemia.
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