Antiangiogenic treatment with endostatin inhibits progression of AML in vivo

• Published in: Leukemia Vol. 19; no. 8; pp. 1312 - 1317
• Main Authors: SCHUCH, G, OLIVEIRA-FERRER, L, LOGES, S, LAACK, E, BOKEMEYER, C, HOSSFELD, D. K, FIEDLER, W, ERGUN, S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01-08-2005; Nature Publishing Group
• Subjects: Acute Disease; Acute myeloid leukemia; Angiogenesis; Angiogenesis inhibitors; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - therapeutic use; Animals; Antiangiogenics; Biological and medical sciences; Bone density; Bone marrow; Bone Marrow Examination; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Cells (biology); Collagen; Density; Drug Compounding; Endostatin; Endostatins - pharmacology; Endostatins - therapeutic use; Gene therapy; Hematologic and hematopoietic diseases; Hematology; Leukemia; Leukemia, Myeloid - drug therapy; Leukemia, Myeloid - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical prognosis; Medical sciences; Mice; Mice, SCID; Microencapsulation; Microspheres; Nanoparticles; Neoplasms, Experimental; Neovascularization, Pathologic - drug therapy; Osteoprogenitor cells; Platelet Endothelial Cell Adhesion Molecule-1 - analysis; Progenitor cells; Solid tumors; Survival Rate; Tumors; Vascular endothelial growth factor; United States > US; Germany; Encapsulation; AML; Hematology; Acute; Endostatin; Malignant hemopathy; Angiogenesis; In vivo; Treatment; Inhibitor; Neovascularization; Antiangiogenic agent; Acute myelocytic leukemia
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2403824

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.