Antiangiogenic therapy for hematologic malignancies

Poor response to therapy and survival in patients with hematologic malignancies has been associated with genetic and molecular abnormalities.^1-9 However, recent evidence highlights the importance of the microenvironment, and potentially, bone marrow angiogenesis (mature endothelial cell-derived generation of new blood vessels) and vasculogenesis (progenitor cell- derived new vessel generation) in the pathophysiology of a number of malignancies, such as acute lymphoblastic leukemia (ALL),^10,11 acute myeloid leukemia (AML),^10,12-20 chronic lymphocytic leukemia (CLL),^10,11,21,22 myelodysplastic syndrome (MDS),^{10,13,16,19,20,23} myeloproliferative disorders,^19,24-30 lymphoma,^11,31,32 multiple myeloma (MM),^11,16,33,34 and possibly Waldenstrom’s macroglobulinemia (WM).^35,36 Several, but not all, studies have also indicated that increased microvessel density (MVD) and proangiogenic factors (e.g., VEGF and bFGF-2) may be associated with an inferior outcome in patients with ALL,^10,11,16,37 AML,^10,13,17,38 agnogenic myeloid metaplasia (AMM),27 CLL,^{10,11,16,22,38} chronic myelomonocytic leukemia (CMML),¹⁰ chronic myeloid leukemia in blastic phase (CML-BP),^10,39 Hodgkin’s lymphoma (HL),31 MDS,^10,13,19,40 MM,^{11,16,33,34,38,41-43} and non- Hodgkin’s lymphoma (NHL).^{11,16,32,38,44} Therefore, evidence supports a clinically significant role for angiogenesis in the pathophysiology of these diseases.