Kalman Filanovsky1*, Michal Haran1*, Vita Mirkin1, Andrei Braester2, Olga Shevetz1, Anfisa Stanevsky1, Erica Sigler1, Ekaterina Votinov1, Yehudit Zaltsman-Amir3, Alain Berrebi1, Atan Gross3 and Lev Shvidel1
1 Hematology Institute, Kaplan medical center, Rehovot, Israel, affiliated with the Hebrew University, Jerusalem, Israel.
2 Hematology institute, Galilee medical center, Nahariya, Israel.
3 Dept. of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
* Both authors equally contributed to this manuscript.
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mitochondrial abnormalities and genetic aberrations in mitochondrial
proteins have been known in Myelodysplastic syndrome (MDS), yet there
is currently little data regarding MDS's metabolic properties and
energy production 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 there is a
significant impairment of mitochondrial respiration in peripheral blood
cells in low-risk MDS, which can be improved with food supplements. We
also show that these supplements may improve the cytopenia and quality
Patients and methods
|Table 1. Clinical characteristics of the patients.|
|Figure 1 Significant improvement in Hemoglobin (Hb) level (red) and decreased need for Packed cell transfusion (blue) in a 56 year old man with MDS with ring sideroblasts following treatment with food supplements.|
|Figure 2. Lower basal and maximal cellular respiration in fresh blood cells obtained from MDS patients as compared to healthy controls. A. OCR measurements of peripheral blood cells obtained from an MDS patient (Red) in comparison to his matched healthy control (blue) under the same conditions. Cells were plated on a Cell-Tak™ coated 24 well XF V7 cell culture microplate at 0.5×106 cells per well in 50 μL of XF assay medium. Each dot represents the average of 3 repeats. B. Results shown are an average of 20 MDS patients and 20 healthy controls comparing the basal respiration (two left columns) and maximal respiration (two right columns) of the healthy controls (Blue) and MDS patients (Red). The error bars represent the standard deviation. Cellular respiration was assessed in fresh blood cells (two hours after collection from the patients at the hospital) using the Seahorse XF analyzer.|
|Figure 3 Increased basal and maximal respiratory capacity in an MDS patient with excess of blasts. OCR measurements of peripheral blood cells obtained from an MDS patient (Red) in comparison to his matched healthy control (blue). Each dot represents the average of 3 repeats. Cells were plated on a Cell-Tak™ coated 24 well XF V7 cell culture microplate at 0.5×106 cells per well in 50 μL of XF assay medium.|
|Figure 4. Improved respiration in fresh blood cells obtained from patients who received food supplements.
Results shown are an average of five MDS patients comparing the Basal
respiration of their blood cells before (Blue) and after (Red)
treatment. The results are presented as the OCR ratio of the MDS
patients to their healthy controls. Cellular respiration was assessed
as described in Figure 1.