Acute myeloid leukemia

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

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References

  1. 1.

    Abdul-Aziz AM, Shafat MS, Mehta TK, Di Palma F, Lawes MJ, Rushworth SA, et al. MIF-induced stromal PKCbeta/IL8 is essential in human acute myeloid leukemia. Cancer Res. 2017;77:303–11.

  2. 2.

    Shafat MS, Oellerich T, Mohr S, Robinson SD, Edwards DR, Marlein CR, et al. Leukemic blasts program bone marrow adipocytes to generate a protumoral microenvironment. Blood. 2017;129:1320–32.

  3. 3.

    Marlein CR, Zaitseva L, Piddock RE, Robinson SD, Edwards DR, Shafat MS, et al. NADPH oxidase-2 derived superoxide drives mitochondrial transfer from bone marrow stromal cells to leukemic blasts. Blood. 2017;130:1649–60.

  4. 4.

    Moschoi R, Imbert V, Nebout M, Chiche J, Mary D, Prebet T, et al. Protective mitochondrial transfer from bone marrow stromal cells to acute myeloid leukemic cells during chemotherapy. Blood. 2016;128:253–64.

  5. 5.

    Fernandez-Marcos PJ, Auwerx J. Regulation of PGC-1alpha, a nodal regulator of mitochondrial biogenesis. Am J Clin Nutr. 2011;93:884S–90.

  6. 6.

    LeBleu VS, O’Connell JT, Gonzalez Herrera KN, Wikman H, Pantel K, Haigis MC, et al. PGC-1alpha mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis. Nat Cell Biol. 2014;16:992–1003,1001–15.

  7. 7.

    Andrzejewski S, Klimcakova E, Johnson RM, Tabaries S, Annis MG, McGuirk S, et al. PGC-1alpha promotes breast cancer metastasis and confers bioenergetic flexibility against metabolic drugs. Cell Metab. 2017;26:778–87. e775

  8. 8.

    Rabinovitch RC, Samborska B, Faubert B, Ma EH, Gravel SP, Andrzejewski S, et al. AMPK maintains cellular metabolic homeostasis through regulation of mitochondrial reactive oxygen species. Cell Rep. 2017;21:1–9.

  9. 9.

    Jager S, Handschin C, St-Pierre J, Spiegelman BM. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci USA. 2007;104:12017–22.

  10. 10.

    Vick B, Rothenberg M, Sandhofer N, Carlet M, Finkenzeller C, Krupka C, et al. An advanced preclinical mouse model for acute myeloid leukemia using patients’ cells of various genetic subgroups and in vivo bioluminescence imaging. PLoS ONE. 2015;10:e0120925.

  11. 11.

    Lou E, Fujisawa S, Morozov A, Barlas A, Romin Y, Dogan Y, et al. Tunneling nanotubes provide a unique conduit for intercellular transfer of cellular contents in human malignant pleural mesothelioma. PLoS ONE. 2012;7:e33093.

  12. 12.

    Lu J, Zheng X, Li F, Yu Y, Chen Z, Liu Z, et al. Tunneling nanotubes promote intercellular mitochondria transfer followed by increased invasiveness in bladder cancer cells. Oncotarget. 2017;8:15539–52.

  13. 13.

    Pasquier J, Guerrouahen BS, Al Thawadi H, Ghiabi P, Maleki M, Abu-Kaoud N, et al. Preferential transfer of mitochondria from endothelial to cancer cells through tunneling nanotubes modulates chemoresistance. J Transl Med. 2013;11:94.

  14. 14.

    Stein EM, DiNardo CD, Pollyea DA, Fathi AT, Roboz GJ, Altman JK, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017;130:722–31.

  15. 15.

    Dinardo CD, Pratz KW, Potluri J, Pullarkat VA, Jonas BA, Wei AH, et al. Durable response with venetoclax in combination with decitabine or azacitadine in elderly patients with acute myeloid leukemia (AML). J Clin Oncol. 2018;36 (suppl): (abstract 7010).

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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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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) doi:10.1038/s41375-018-0221-y

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