Antiangiogenic treatment with endostatin inhibits progression of AML in vivo

Abstract

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.

Bone marrow angiogenesis magnetic resonance imaging in patients with acute myeloid leukemia: peak enhancement ratio is an independent predictor for overall survival

“…15,16,41 This has prompted novel antiangiogenic approaches in AML. 41,[48][49][50] However, to assess the angiogenic changes in patients with AML and monitor clinical effects of such antiangiogenic therapy requires a new and promising strategy. The current study's finding that DCE-MRI assessment of patients with AML with increased bone marrow angiogenesis can predict poor clinical outcome also indicates that antiangiogenesis treatment may be beneficial for these patients.…”

The Role of VEGF and EGFR Inhibition: Implications for Combining Anti–VEGF and Anti–EGFR Agents

“…Pathologic angiogenesis is critical to the growth (by providing oxygen and other nutrients) and malignant dissemination (providing a route for metastases) of solid tumors (10)(11)(12)(13). Angiogenesis also contributes to the development of hematologic malignancies, particularly multiple myeloma, leukemia, and lymphoma, although the role of angiogenesis has not been as clearly defined in hematologic malignancies and might vary in lymphoma subtypes (14)(15)(16). VEGF binds primarily to receptors on endothelial cells but may also act on tumor (3), hematopoietic (17), and neural cells (18).…”

Elevated serum endostatin levels is associated with favorable outcome in acute myeloid leukemia

“…This fi nding raises the possibility that endostatin may be used in AML therapy. In support of this opinion is the fi nding reported by Schuch et al [21] who stated that endostatin microbeads signifi cantly inhibits growth of subcutaneous choloromas in SCID mice as compared to controls. In a leukemia model using M1 cells the concomitant treatment of mice with EEs microbeads prolonged median survival signifi cantly.…”