Influence of diet and metabolism on hematopoietic stem cells and leukemia development following ionizing radiation exposure

Abstract

Purpose: The review aims to discuss the prominence of dietary and metabolic regulators in maintaining hematopoietic stem cell (HSC) function, long-term self-renewal, and differentiation.

Results: Most adult stem cells are preserved in a quiescent, nonmotile state in vivo which acts as a “protective state” for stem cells to reduce endogenous stress provoked by DNA replication and cellular respiration as well as exogenous environmental stress. The dynamic balance between quiescence, self-renewal and differentiation is critical for supporting a functional blood system throughout life of an organism. Stress-conditions, for example ionizing radiation exposure can trigger the blood forming HSCs to proliferate and migrate through extramedullary tissues to expand the number of HSCs and increase hematopoiesis. In addition, a wealth of investigation validated that deregulation of this balance plays a critical pathogenic role in various different hematopoietic diseases including the leukemia development.

Conclusion: The review summarizes the current knowledge on how alterations in dietary and metabolic factors could alter the risk of leukemia development following ionizing radiation exposure by inhibiting or even reversing the leukemic progression. Understanding the influence of diet, metabolism, and epigenetics on radiation-induced leukemogenesis may lead to the development of practical interventions to reduce the risk in exposed populations.

Keywords:

• HSC
• leukemia
• ionizing radiation
• diet
• metabolism

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Melis Karabulutoglu would like to acknowledge the support of PHE for funding DPhil studentship.

Notes on contributors

Melis Karabulutoglu

Melis Karabulutoglu joined Cancer Mechanisms and Biomarkers group as a DPhil student (January 2018) under supervision of Dr. Badie on a joint degree programme with the University of Oxford. Her PhD project focuses on investigating the mechanisms of radiation leukaemogenesis, characterisation of the haematopoietic stem cells and modulation of the risk.

Rosemary Finnon

Rosemary Finnon is a Principal Radiation Protection Scientist in the Cancer Mechanisms and Biomarkers group led by Dr. Christophe Badie at PHE CRCE. She has co-authored 16 peer-reviewed publications on the chromosomal and molecular mechanisms that underlie radiation-induced Acute Myeloid Leukaemogenesis in the mouse.

Tatsuhiko Imaoka

Tatsuhiko Imaoka was a Researcher, Senior Researcher and Team Leader at the National Institute of Radiological Sciences from 2002 until 2016. He is now is a Team Leader at the National Institutes for Quantum and Radiological Science and Technology.

Anna A. Friedl

Anna A. Friedl is Adjunct Professor for Human Genetics at the University of Munich. She co-authored more than 100 publications on molecular radiation biology, DNA repair, epigenetic effects, and personalized radiotherapy. She is a member of the German delegation to UNSCEAR and Deputy President of the German Commission for Radiation Protection (SSK).

Christophe Badie

Christophe Badie is the head of the Cancer Mechanisms and Biomarkers group of Public Health England. He co-authored more than 70 publications on DNA repair, radiation leukaemogenesis, radiation biomarkers. He is a member of the Association for Radiation Research committee and its treasurer. He gives lectures at Oxford University.