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
Main Article Content
Keywords
myelodysplastic syndrome, mitochondria, oxidative phosphorylation, coenzyme Q10, seahorse XF analyzer.
Abstract
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.
Downloads
Abstract 538
PDF Downloads 545
HTML Downloads 185
References
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.
Article Sidebar
Article Details
How to Cite
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers. Authors will grant copyright of their articles to the Institute of Hematology, Catholic University, Rome . No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.
Michal Haran, 1. Hematology Institute, Kaplan medical center, Rehovot, Israel; affiliated with the Hebrew university, Jerusalem, Israel
Author had equivalent role in manuscript preparation as first author