Anti-Angiogenic Therapies in the Treatment of Waldenstrom's Macroglobulinemia

A.      Sacco; I.      M. Ghobrial; A.      M. Roccaro

Abstract

Bone marrow microenvironment has been shown to play a crucial role in supporting the pathogenesis and the progression of several B-cell malignancies, including Waldenstrom's Macroglobulinemia (WM). Among the different cell types within the bone marrow milieu, endothelial cells have been proven to support WM cells growth. Based on the understanding of bone marrow neo-angiogenesis in plasma cell dyscrasias, a number of anti-angiogenic molecules are now available for the treatment of these diseases. Indeed, anti-angiogenic drugs, such as proteasome-, proteins kinase-C (PKC)-, phosphatidylinositol 3-kinase/mammalian target of rapamycin (mTOR)-, and histone deacetylase (HDAC)- inhibitors are now available, playing a key role in the treatment of WM both in the preclinical settings and as part of clinical trials.

Keywords: Anti-angiogenic approach, Waldenstrom's Macroglobulinemia, B-cell malignancies, endothelial cells, plasma cell, proteins kinase-C, lymphoplasmacytic cells, Chromosomal, angiogenin, VEGF-A, bortezomib, interleukin-6