TY - JOUR
T1 - Application of vitamin D and vitamin D analogs in acute myelogenous leukemia
AU - Cao, Huynh
AU - Xu, Yi
AU - de Necochea-Campion, Rosalia
AU - Baylink, David J.
AU - Payne, Kimberly J.
AU - Tang, Xiaolei
AU - Ratanatharathorn, Christina
AU - Ji, Yong
AU - Mirshahidi, Saied
AU - Chen, Chien Shing
N1 - Publisher Copyright:
© 2017 ISEH - International Society for Experimental Hematology
PY - 2017/6
Y1 - 2017/6
N2 - Acute myeloid leukemia (AML) is characterized by the accumulation of malignant, transformed immature hematopoietic myeloid precursors that have lost their ability to differentiate and proliferate normally. Current treatment for AML requires intensive cytotoxic chemotherapy and results in significant morbidity and mortality, especially in older patients. Effective and better-tolerated treatment is urgently needed. Studies have shown that 1α,25-dihydroxyvitamin D3 (1,25-D3, active VD3) or vitamin D analogs (VDAs) can potently differentiate AML cells in vitro and ex vivo, which led to early clinical trials in AML and myelodysplastic syndrome patients. However, one major limiting factor in the clinical application of active VD3 or VDAs is the supraphysiologic dose required, which results in systemic hypercalcemia. Several important questions (i.e., dosage, method of delivery, metabolism of 1,25-D3 in situ, systemic hypercalcemia, and mechanisms of action of combination treatment) have to be addressed before vitamin D treatment can be applied to the clinical setting. This review focuses on 1,25-D3's mechanism of action in AML, preclinical data, and clinical trial outcomes, with an emphasis on major roadblocks to successful trials and suggestions for future directions.
AB - Acute myeloid leukemia (AML) is characterized by the accumulation of malignant, transformed immature hematopoietic myeloid precursors that have lost their ability to differentiate and proliferate normally. Current treatment for AML requires intensive cytotoxic chemotherapy and results in significant morbidity and mortality, especially in older patients. Effective and better-tolerated treatment is urgently needed. Studies have shown that 1α,25-dihydroxyvitamin D3 (1,25-D3, active VD3) or vitamin D analogs (VDAs) can potently differentiate AML cells in vitro and ex vivo, which led to early clinical trials in AML and myelodysplastic syndrome patients. However, one major limiting factor in the clinical application of active VD3 or VDAs is the supraphysiologic dose required, which results in systemic hypercalcemia. Several important questions (i.e., dosage, method of delivery, metabolism of 1,25-D3 in situ, systemic hypercalcemia, and mechanisms of action of combination treatment) have to be addressed before vitamin D treatment can be applied to the clinical setting. This review focuses on 1,25-D3's mechanism of action in AML, preclinical data, and clinical trial outcomes, with an emphasis on major roadblocks to successful trials and suggestions for future directions.
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U2 - 10.1016/j.exphem.2017.01.007
DO - 10.1016/j.exphem.2017.01.007
M3 - Review article
C2 - 28174131
SN - 0301-472X
VL - 50
SP - 1
EP - 12
JO - Experimental Hematology
JF - Experimental Hematology
ER -