Energy metabolism and drug response in myeloid leukaemic stem cells

Br J Haematol. 2019 Aug;186(4):524-537. doi: 10.1111/bjh.16074. Epub 2019 Jun 24.

Abstract

Despite significant advances in the treatment of myeloid malignancies, many patients become resistant to therapy and ultimately succumb to their disease. Accumulating evidence over the past several years has suggested that the inadequacy of many leukaemia therapies results from their failure to target the leukaemic stem cell (LSC). For this reason, the LSC population currently represents the most critical target in the treatment of myeloid malignancies. However, while LSCs are ideal targets in the treatment of these diseases, they are also the most difficult population to target. This is due to both their heterogeneity within the LSC population, and also their phenotypic similarities with normal haematopoietic stem cells. This review will highlight the current landscape surrounding LSC biology in myeloid malignancies, with a focus on altered energy metabolism, and how that knowledge is being translated into clinical advances for the treatment of chronic and acute myeloid leukaemia and myelodysplastic syndromes.

Keywords: acute myeloid leukaemia; cancer stem cell; chronic myeloid leukaemia; leukaemic stem cell; myelodysplastic syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor
  • Clinical Trials as Topic
  • Drug Resistance, Neoplasm / genetics
  • Energy Metabolism*
  • Hematopoiesis
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Leukemia, Myeloid / diagnosis
  • Leukemia, Myeloid / drug therapy
  • Leukemia, Myeloid / etiology*
  • Leukemia, Myeloid / metabolism*
  • Myelodysplastic Syndromes / diagnosis
  • Myelodysplastic Syndromes / etiology
  • Myelodysplastic Syndromes / metabolism
  • Myelodysplastic Syndromes / therapy
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / metabolism*
  • Signal Transduction
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor