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Vitamin D and Leukaemia

  • Geoffrey Brown
  • Andrzej Kutner
  • Ewa Marcinkowska
Chapter
Part of the Contemporary Endocrinology book series (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.

Keywords

Leukaemia Vitamin D Vitamin D analogues Differentiation therapy Acute myeloid leukaemia Myelodysplastic syndrome 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Geoffrey Brown
    • 1
  • Andrzej Kutner
    • 2
  • Ewa Marcinkowska
    • 3
  1. 1.Institute of Clinical Sciences, Institute of Immunology and Immunotherapy, College of Medical and Dental SciencesUniversity of Birmingham EdgbastonBirminghamUK
  2. 2.Department of PharmacologyPharmaceutical Research InstituteWarsawPoland
  3. 3.Laboratory of Protein Biochemistry, Faculty of BiotechnologyUniversity of WroclawWroclawPoland

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