Journal
LEUKEMIA RESEARCH
Volume 34, Issue 5, Pages 553-565Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2009.09.010
Keywords
Vitamin D-3; Deltanoids; Leukemia; Differentiation therapy; Cell signaling
Categories
Funding
- NIH [RO1 CA 44722, 5RO1 119242]
- Polish Ministry of Science and Higher Education [2622/P01/2006/31, 2132/B/P01/2008/34]
- NATIONAL CANCER INSTITUTE [R01CA044722] Funding Source: NIH RePORTER
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Primitive myeloid leukemic cell lines can be driven to differentiate to monocyte-like cells by 1 alpha,25-dihydroxyvitaminD(3) (1,25(OH)(2)D-3), and, therefore, 1,25(OH)(2)D-3 may be useful in differentiation therapy of myeloid leukemia and myelodysplastic syndromes (MDS). Recent studies have provided important insights into the mechanism of 1,25(OH)(2)D-3-stimulated differentiation. For myeloid progenitors to complete monocytic differentiation a complex network of intracellular signals has to be activated and/or inactivated in a precise temporal and spatial pattern. 1,25(OH)(2)D-3 achieves this change to the 'signaling landscape' by (i) direct genomic modulation of the level of expression of key regulators of cell signaling and differentiation pathways, and (ii) activation of intracellular signaling pathways. An improved understanding of the mode of action of 1,25(OH)(2)D-3 is facilitating the development of new therapeutic regimens. (C) 2009 Elsevier Ltd. All rights reserved.
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