NADPH oxidase-2 derived superoxide drives mitochondrial transfer from bone marrow stromal cells to leukemic blasts

Marlein, Christopher R., Zaitseva, Lyubov, Piddock, Rachel E., Robinson, Stephen ORCID: https://orcid.org/0000-0002-6606-7588, Edwards, Dylan ORCID: https://orcid.org/0000-0002-3292-2064, Shafat, Manar S., Zhou, Zhigang, Lawes, Matthew, Bowles, Kristian M. ORCID: https://orcid.org/0000-0003-1334-4526 and Rushworth, Stuart A. (2017) NADPH oxidase-2 derived superoxide drives mitochondrial transfer from bone marrow stromal cells to leukemic blasts. Blood, 130 (14). pp. 1649-1660. ISSN 0006-4971

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Abstract

Improvements in the understanding of the metabolic cross-talk between cancer and its micro-environment are expected to lead to novel therapeutic approaches. Acute myeloid leukemia (AML) cells have increased mitochondria compared to non-malignant CD34+ hematopoietic progenitor cells. Furthermore, contrary to the Warburg hypothesis, (AML) relies on oxidative phosphorylation to generate ATP. Here we report that in human AML, NOX2 generates superoxide which stimulates bone marrow stromal cells (BMSC) to AML blast transfer of mitochondria through AML derived tunnelling nanotubes. Moreover, inhibition of NOX2 was able to prevent mitochondrial transfer, increase AML apoptosis and improve NSG AML mouse survival. Although mitochondrial transfer from BMSC to non-malignant CD34+ cells occurs in response to oxidative stress, NOX2 inhibition had no detectable effect on non-malignant CD34+ cell survival. Taken together we identify tumor-specific dependence on NOX2 driven mitochondrial transfer as a novel therapeutic strategy in AML.

Item Type:	Article
Uncontrolled Keywords:	sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science > School of Biological Sciences Faculty of Science
UEA Research Groups:	Faculty of Science > Research Groups > Cells and Tissues Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User:	Pure Connector
Date Deposited:	28 Jul 2017 05:07
Last Modified:	24 Oct 2023 00:56
URI:	https://ueaeprints.uea.ac.uk/id/eprint/64291
DOI:	10.1182/blood-2017-03-772939

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