Increased vessel density in the bone marrow of patients with acute myeloid 
leukemia as well as elevated expression of proangiogenic factors by leukemic 
cells implies a central role of angiogenesis in hematological malignancies. 
Endostatin (ES), a fragment of collagen XVIII, is an endogenous inhibitor of 
angiogenesis that has shown therapeutic activity in solid tumors in various 
preclinical models. Using microencapsulation technology, we studied the 
therapeutic effect of ES in AML. While ES had no effect on proliferation of M1 
murine leukemic cells in vitro, ES producing microbeads significantly inhibited 
growth of subcutaneous chloromas in SCID mice as compared to controls. In a 
leukemia model using M1 cells the concomitant treatment of mice with ES 
microbeads prolonged median survival significantly. Histological analysis 
revealed a decreased microvessel density and a reduced number of CD31-positive 
single cells, putatively endothelial progenitor cells, in the bone marrow of 
treated animals. Taken together, ES has inhibitory effects on neo-angiogenesis 
in the bone marrow and on progression of leukemia in vivo. These experiments 
suggest a possible therapeutic role of antiangiogenic gene therapy with ES in 
AML.