Page 264 - Vitamin D and Cancer

Chapter 11
Vitamin D and Hematologic Malignancies

Ryoko Okamoto, Tadayuki Akagi, and H. Phillip Koeffler

Abstract The biologically active form of vitamin D, 1,25-dihydroxyvitamin D
3
[1,25(OH) D ], has multiple anticancer activities including growth arrest, induction
3
2
of apoptosis, and differentiation. Here, the actions of vitamin D compounds are
addressed from normal to malignant hematopoietic cells. The effects are driven by
binding of vitamin D to vitamin D receptor in either genomic and/or nongenomic
fashions. However, its application as a therapeutic agent is limited by its side
effect, hypercalcemia. 1,25(OH) D analogs have been synthesized to obtain anti-
3
2
tumor activity with less calcemic toxicity. Limited clinical studies using vitamin
D compounds have had only minor clinical success for patients with leukemia or
myelodysplasia syndrome. Nevertheless, preclinical studies suggest that the combi-
nation of vitamin D compounds with other agents can have additive or synergistic
anticancer activities, renewing hope for future clinical studies.

Keywords Hematopoiesis • Vitamin D • Vitamin D receptor • Leukemia
• Molecular mechanisms • Vitamin D analogs • Combination therapy

11.1 Overview of Hematopoiesis

Hematopoiesis is the process that leads to the formation of the highly specialized
circulating blood cells from pluripotent hematopoietic stem cells (HSCs) in the bone
marrow. The HSCs are the most primitive blood cells, and they have the ability for
both self-renewal and pluripotency. They differentiate to more mature “committed”
cells including the common lymphoid progenitor (CLP) and the common myeloid
progenitor (CMP); and the latter differentiates to megakaryocyte-erythroid progenitors

R. Okamoto (*)
Division of Hematology and Oncology,
Cedars-Sinai Medical Center, UCLA School of Medicine,
8700 Beverly Blvd, Los Angeles, CA 90048, USA
e-mail: ryoko.okamoto@cshs.org

D.L. Trump and C.S. Johnson (eds.), Vitamin D and Cancer, 251
DOI 10.1007/978-1-4419-7188-3_11, © Springer Science+Business Media, LLC 2011