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Extraskeletal Effects of Vitamin D pp 115–134Cite as

Vitamin D and Leukaemia

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Part of the book series: Contemporary Endocrinology ((COE))

Abstract

The most active vitamin D metabolite is 1α,25-dihydroxyvitamin D3. This agent is able to drive growth arrest and differentiation of a wide variety of cancer cells, including the differentiation of acute myeloid leukaemia cells towards macrophage-like cells. For 30 years there has been an interest in using 1α,25-dihydroxyvitamin D3 for differentiation therapy of acute leukaemia and other cancers. Despite strong support from the findings from preclinical studies, clinical trials, conducted in myelodysplastic syndrome and acute myeloid leukaemia, have resulted in conflicting and often disappointing results. A main barrier to the use of 1α,25-dihydroxyvitamin D3 is that it is difficult to achieve an effective therapeutic dose which is severely limited by a calcaemic action. The way forward to resolving this problem has been the development of a number of analogues that have a lowered calcaemic action and that retain their differentiating activity against leukaemia cells. In particular, new analogues of 1α,25-dihydroxyvitamin D3 and 1α,25-dihydroxyvitamin D2 have been synthesised with a substantially reduced calcaemic action that are more potent in differentiating acute myeloid leukaemia cells than 1α,25-dihydroxyvitamin D3. The benefit or otherwise of the use of vitamin D analogues, alone or in combination with conventional chemotherapy, to treat patients with leukaemia and other cancers, is far from resolved. Recently synthesised potent and low-calcaemic analogues offer the exciting prospect of new regimes for differentiation therapy of leukaemia.

Acknowledgements

This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 315902. GB, AK and EM are partners within the Marie Curie Initial Training Network DECIDE (Decision-making within cells and differentiation entity therapies). The research of EM was supported by National Science Centre, Poland (grant No 2015/17/B/NZ4/02632).

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Authors and Affiliations

  1. Institute of Clinical Sciences, Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham Edgbaston, Birmingham, UK

    Geoffrey Brown BSc, PhD

  2. Department of Pharmacology, Pharmaceutical Research Institute, Warsaw, Poland

    Andrzej Kutner BSc, PhD, DSc

  3. Laboratory of Protein Biochemistry, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland

    Ewa Marcinkowska MD, PhD

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  1. Geoffrey Brown BSc, PhD
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  3. Ewa Marcinkowska MD, PhD
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Correspondence to Geoffrey Brown BSc, PhD .

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  1. Lenox Hill Hospital, New York, New York, USA

    Emilia Pauline Liao

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Brown, G., Kutner, A., Marcinkowska, E. (2018). Vitamin D and Leukaemia. In: Liao, E. (eds) Extraskeletal Effects of Vitamin D. Contemporary Endocrinology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-73742-3_6

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