Hematological malignancy

Abstract

Hematopoiesis is the process that leads to the regulated formation of the highly specialized circulating blood cells from pluripotent hematopoietic stem cells (HSCs) in the bone marrow. This chapter focuses on the interaction of 1,25(OH)2D3 with the normal and the malignant hematopoietic system, especially examining the ability of this secosteroid to induce differentiation and inhibit proliferation of normal and leukemic myeloid cells. It also discusses the development and testing in vitro and in vivo of vitamin D analogs. The secosteroid hormone 1,25(OH)2D3 has a role in normal hematopoiesis, enhancing the activity of monocyte-macrophage differentiation. It also has anti-proliferative and pro-differentiation effects against various myeloid leukemia cell lines by both genomic and nongenomic pathways. Nevertheless, hematopoiesis in vitamin D3 receptor deletional mice is fairly normal, suggesting the vitamin D3 pathway has an adjunctive role in blood formation in mammals. Although these compounds, used either alone or combined with other agents, have preclinical activity, their efficacy in clinical trials has thus far appeared to be limited. © 2011 Elsevier Inc. All rights reserved.