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Acute myeloid leukemia

PGC-1α driven mitochondrial biogenesis in stromal cells underpins mitochondrial trafficking to leukemic blasts

Leukemia volume 32, pages 2073–2077 (2018)Cite this article

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Acute myeloid leukemia (AML) is a disease known to be heavily reliant on its bone microenvironment to survive and proliferate [1, 2]. We have previously shown that AML disease progression is enabled by the transfer of functional mitochondria to the malignant cell from bone marrow stromal cells (BMSC) [3, 4]. This process was shown to be stimulated by superoxide generated by NADPH oxidase-2 (NOX2) on the AML blast [3]. However, beyond the stimulation of reactive oxygen species in BMSC, the mechanisms controlling mitochondrial transfer in BMSC have yet to be elucidated.

There are no apparent adverse effects on BMSC after donation of mitochondria to AML blasts, implying the presence of a mechanism whereby the BMSC can recover their metabolic potential. The master regulator of mitochondrial biogenesis [5], peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), has been implicated in cancer progression and metabolism [6, 7]. In these studies, PGC-1α is up-regulated and causes an increased accumulation of functional mitochondria. Here, we investigate the effect AML has on the mitochondrial mass, bio-energetic potential, and PGC-1α expression in BMSC.

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Acknowledgements

The authors thank the Rosetrees Trust and the Norwich Research Park Doctoral Training Program for funding. They also thank Professor Richard Ball, Dr. Mark Wilkinson, Mr. Iain Sheriffs, and Ms. Sue Steel, Norwich Biorepository (UK) for help with sample collection and storage. pCDH-luciferase-T2A-mCherry was kindly gifted by Professor Irmela Jeremias, MD, from Helmholtz Zentrum München, Munich, Germany. The authors also thank Dr. Allyson Tyler, Dr. Ian Thirkettle, and Dr. Karen Ashurst from the Laboratory Medicine Department at the Norfolk and Norwich University Hospital for technical assistance.

Authorship contributions

CRM, KMB. and SAR designed the research; CRM performed the research; CRM and REP carried out in vivo work; LZ, LRB, MAS, CJI, AC, and KMB provided essential knowledge and reagents; CRM, KMB, and SAR wrote the paper

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Authors and Affiliations

  1. Department of Molecular Haematology, Norwich Medical School, The University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK

    Christopher R. Marlein, Lyubov Zaitseva, Rachel E. Piddock, Kristian M. Bowles & Stuart A. Rushworth

  2. Haematopathology and Oncology Diagnostic Service, Addenbrooke’s Hospital, Hills Rd, Cambridge, CB2 0QQ, UK

    Livia Raso-Barnett & Michael A. Scott

  3. Department of Trauma and Orthopaedic Surgery, Norfolk and Norwich University Hospitals NHS Trust, Colney Lane, Norwich, NR4 7UY, UK

    Christopher J. Ingham

  4. Department of Haematology, Norfolk and Norwich University Hospitals NHS Trust, Colney Lane, Norwich, NR4 7UY, UK

    Angela Collins & Kristian M. Bowles

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  1. Christopher R. Marlein
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  2. Lyubov Zaitseva
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  3. Rachel E. Piddock
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  4. Livia Raso-Barnett
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  6. Christopher J. Ingham
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  7. Angela Collins
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  8. Kristian M. Bowles
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Corresponding authors

Correspondence to Kristian M. Bowles or Stuart A. Rushworth.

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Marlein, C.R., Zaitseva, L., Piddock, R.E. et al. PGC-1α driven mitochondrial biogenesis in stromal cells underpins mitochondrial trafficking to leukemic blasts. Leukemia 32, 2073–2077 (2018). https://doi.org/10.1038/s41375-018-0221-y

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