Original Articles
Vol. 12 No. 1 (2020): Mediterranean Journal of Hematology and Infectious Diseases, Volume 12, 2020
PERPHERAL BLOOD CELL MITOCHONDRIAL DYSFUNCTION IN MYELODYSPLASTIC SYNDROMECAN BE IMPROVED BY A COMBINATION OF COENZYME Q10 AND CARNITINE
Blood cell mitochondrial dysfunction in myelodysplastic syndrome
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Received: June 27, 2020
Accepted: September 29, 2020
Accepted: September 29, 2020
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Structural mitochondrial abnormalities as well as genetic aberrations in mitochondrial proteins have been known in Myelodysplastic syndrome (MDS) , yet there is currently little data regarding the metabolic properties and energy production of MDS cells. In the current study we used state-of-the-art methods to assess OXPHOS in peripheral blood cells obtained from MDS patients and healthy controls We then assessed the effect of food supplements- Coenzyme Q10 and carnitine on mitochondrial function and hematological response .We show here for the first time that in low risk MDS there is a significant impairment of mitochondrial respiration in peripheral blood cells and this can be improved with food supplements. We also show that such myelodysplastic syndrome, mitochondria, oxidative phosphorylation, coenzyme Q10, seahorse XF analyzer. supplements lead to improvement in cytopenia's and quality of life.
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Citations
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2. Haran M, Gross A. Balancing glycolysis and mitochondrial OXPHOS: lessons from the hematopoietic system and exercising muscles. Mitochondrion 2014;19 Pt A3–7.
3. Cheson BD, GreenbergPl,BennettJM,Clinical application and proposal for modification of the International Working Group(IWG) response creteria in myelodisplasia.Blood 2006;108:419-5.
4. Sadighara M, Joktaji J.P, Hajhashemi V,et al. Protective effects of coenzyme Q10 and
L-carnitine against statin-induced pancreatic mitochondrial toxicity in rats. Res Pharm Sci.2017;12:434-43.
5. Kulasekararaj AG, Mohamedali AM, Mufti GJ. Recent advances in understanding the molecular pathogenesis of myelodysplastic syndromes. British journal of haematology;162:587-605
6. Fenaux P, Santini V, Spiriti MAA, et al. A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-? in anemic patients with low-risk MDS. Leukemia 2018;32:2648–2658.
7.Greenberg PL, Sun Z, Miller KB, et al. Treatment of myelodysplastic syndrome patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase 3 trial by the Eastern Cooperative Oncology Group (E1996). Blood 2009;114:2393–2400.
8. Shlush LI. Change comes like a little wind: tales in MDS evolution. Blood 2016;128:1162–3
9. van de Loosdrecht AA, Brada SJ, Blom NR, et al. Mitochondrial disruption and limited apoptosis of erythroblasts are associated with high risk myelodysplasia. An ultrastructural analysis. Leuk Res 2001;25:385–93.
10. Gattermann N. From sideroblastic anemia to the role of mitochondrial DNA mutations in myelodysplastic syndromes. Leuk Res 2000;24:141–151.
11. Schildgen V, Wulfert M, Gattermann N. Impaired mitochondrial gene transcription in myelodysplastic syndromes and acute myeloid leukemia with myelodysplasia-related changes. Exp Hematol 2011;39:666–75.e1.
12. Bowen D, Peddie C. Mitochondrial oxygen consumption and ineffective haematopoiesis in patients with myelodysplastic syndromes. Br J Haematol 2002;11:345–346.
13. Quinzii CM, Hirano M. Coenzyme Q and mitochondrial disease. Dev Disabil Res Rev 2010;16:183–188.
14. Nicolson GL, Conklin ÆKA. Reversing mitochondrial dysfunction , fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy. Clin Exp Metastasis 2008;161–169.
15. Galili N, Sechman E V, Cerny J, et al. Clinical response of myelodysplastic syndromes patients to treatment with coenzyme Q10. Leuk Res 2007;31:19–26.
16. Liyanage SU, Hurren R, Voisin V, et al. Leveraging increased cytoplasmic nucleoside kinase activity to target mtDNA and oxidative phosphorylation in AML. Blood 2017;129:2657–66.
17. Mohamedali AM, Alkhatabi H, Kulasekararaj A, et al. Utility of peripheral blood for cytogenetic and mutation analysis in myelodysplastic syndrome. Blood 2013;122:567–70.
18. Brandenburg NA, Yu R, Revicki DA. Reliability and Validity of the FACT-AN In Patients with Low or Int-1-Risk Myelodysplastic Syndromes with Deletion 5q. Blood;116:3827
19. an der Windt GJW, Chang C-H, Pearce EL. Measuring Bioenergetics in T Cells Using a Seahorse Extracellular Flux Analyzer. In: Current Protocols in Immunology. Hoboken, NJ, USA: John Wiley & Sons, Inc.; 2016. p3.16B.1-3.16B.14.
2. Haran M, Gross A. Balancing glycolysis and mitochondrial OXPHOS: lessons from the hematopoietic system and exercising muscles. Mitochondrion 2014;19 Pt A3–7.
3. Cheson BD, GreenbergPl,BennettJM,Clinical application and proposal for modification of the International Working Group(IWG) response creteria in myelodisplasia.Blood 2006;108:419-5.
4. Sadighara M, Joktaji J.P, Hajhashemi V,et al. Protective effects of coenzyme Q10 and
L-carnitine against statin-induced pancreatic mitochondrial toxicity in rats. Res Pharm Sci.2017;12:434-43.
5. Kulasekararaj AG, Mohamedali AM, Mufti GJ. Recent advances in understanding the molecular pathogenesis of myelodysplastic syndromes. British journal of haematology;162:587-605
6. Fenaux P, Santini V, Spiriti MAA, et al. A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-? in anemic patients with low-risk MDS. Leukemia 2018;32:2648–2658.
7.Greenberg PL, Sun Z, Miller KB, et al. Treatment of myelodysplastic syndrome patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase 3 trial by the Eastern Cooperative Oncology Group (E1996). Blood 2009;114:2393–2400.
8. Shlush LI. Change comes like a little wind: tales in MDS evolution. Blood 2016;128:1162–3
9. van de Loosdrecht AA, Brada SJ, Blom NR, et al. Mitochondrial disruption and limited apoptosis of erythroblasts are associated with high risk myelodysplasia. An ultrastructural analysis. Leuk Res 2001;25:385–93.
10. Gattermann N. From sideroblastic anemia to the role of mitochondrial DNA mutations in myelodysplastic syndromes. Leuk Res 2000;24:141–151.
11. Schildgen V, Wulfert M, Gattermann N. Impaired mitochondrial gene transcription in myelodysplastic syndromes and acute myeloid leukemia with myelodysplasia-related changes. Exp Hematol 2011;39:666–75.e1.
12. Bowen D, Peddie C. Mitochondrial oxygen consumption and ineffective haematopoiesis in patients with myelodysplastic syndromes. Br J Haematol 2002;11:345–346.
13. Quinzii CM, Hirano M. Coenzyme Q and mitochondrial disease. Dev Disabil Res Rev 2010;16:183–188.
14. Nicolson GL, Conklin ÆKA. Reversing mitochondrial dysfunction , fatigue and the adverse effects of chemotherapy of metastatic disease by molecular replacement therapy. Clin Exp Metastasis 2008;161–169.
15. Galili N, Sechman E V, Cerny J, et al. Clinical response of myelodysplastic syndromes patients to treatment with coenzyme Q10. Leuk Res 2007;31:19–26.
16. Liyanage SU, Hurren R, Voisin V, et al. Leveraging increased cytoplasmic nucleoside kinase activity to target mtDNA and oxidative phosphorylation in AML. Blood 2017;129:2657–66.
17. Mohamedali AM, Alkhatabi H, Kulasekararaj A, et al. Utility of peripheral blood for cytogenetic and mutation analysis in myelodysplastic syndrome. Blood 2013;122:567–70.
18. Brandenburg NA, Yu R, Revicki DA. Reliability and Validity of the FACT-AN In Patients with Low or Int-1-Risk Myelodysplastic Syndromes with Deletion 5q. Blood;116:3827
19. an der Windt GJW, Chang C-H, Pearce EL. Measuring Bioenergetics in T Cells Using a Seahorse Extracellular Flux Analyzer. In: Current Protocols in Immunology. Hoboken, NJ, USA: John Wiley & Sons, Inc.; 2016. p3.16B.1-3.16B.14.
Supporting Agencies
Acknowledgments: we are grateful to Haim Aviv PhD for his help in design of the research and donation of the food supplements., Funding: This study was funded by a grants from the Rising Tide foundation and Israel Society of Hematology and Blood transfusion.How to Cite
“PERPHERAL BLOOD CELL MITOCHONDRIAL DYSFUNCTION IN MYELODYSPLASTIC SYNDROMECAN BE IMPROVED BY A COMBINATION OF COENZYME Q10 AND CARNITINE: Blood cell mitochondrial dysfunction in myelodysplastic syndrome” (2020) Mediterranean Journal of Hematology and Infectious Diseases, 12(1), p. e2020072. doi:10.4084/mjhid.2020.072.
Copyright (c) 2020 Kalman Filanovsky, Michal Haran, Vita Mirkin, Andrei Braester, Olga Shevetz, Anfisa Stanevsky, Erica Sigler, Ekaterina Votinov, Yehudit Zalzman-Amir, Alain Berrebi, Atan Gross, Lev Shvidel
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
