Lelcu 2019 MiP2019

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Theia Lelcu
Assessment of platelet respiration in blood malignancies: a pilot study in children and adults.

Link: MiP2019

Lelcu T, Bina AM, Avram VF, Aburel OM, Borza C, Arghirescu S, Muntean DM (2019)

Event: MiP2019


Assessment of respiration function in circulating cells has recently emerged as the peripheral biomarker of the overall metabolic health [1] that improve our understanding of the pathophysiology of diseases associated with mitochondrial dysfunction [2]. Impaired mitochondrial bioenergetics has been recently reported to occur in platelets isolated from patients with haematological malignancies and chemotherapy-induced thrombocytopenia [3]. Whether changes in mitochondrial respiration occur early in these pathologies it is not known.

The present study was double-aimed: i) to characterize platelet mitochondrial respiration in consecutive patients with newly diagnosed blood malignancies, and ii) to assess the effect of plasma belonging to these patients on platelets isolated from healthy volunteers.

Blood samples were taken in K2EDTA tubes via venous puncture in from adult and pediatric patients with leukemias and lymphomas. The platelet pellet was freshly prepared by a two-step centrifugation at room temperature, resuspended in patient own' plasma and further used for high-resolution respirometry studies at 37ยฐC using the Oxygraph-2k (Oroboros Instruments, Innsbruck, Austria). Respiratory function of isolated platelets (50 x 106 cells/mL) was assessed after membrane permeabilization with digitonin according to a classic Substrate-Uncoupler-Inhibitor-Titration (SUIT) protocol. After stabilization at the routine state, the following respiratory parameters were measured: active respiration (OXPHOS state, CI and CII-supported), basal, ADP-independent respiration (State 4, oligomycin-induced), and maximal uncoupled respiration or the electron transport system capacity (ETS state, FCCP-induced). The non-mitochondrial, residual oxygen consumption (ROX) was subtracted from all respiratory rates for data analysis. In a different set of experiments, platelets isolated from healthy donors were resuspended in plasma from patients with blood malignancies and underwent the same SUIT protocol.

Preliminary data showed a significant decrease in both CI and CII-dependent OXPHOS and ETS in adult but not in pediatric patients with acute leukemias and lymphomas at the onset of disease (the moment of first diagnostic). Moreover, plasma isolated from these patients impaired the respiratory function of platelets harvested from healthy volunteers.

Platelet mitochondrial respiration is early impaired in adults with blood malignancies and plasma of these patients appears to elicit toxic effects on healthy mitochondria. Experiments are ongoing to further assess the effects of chemotherapy regimens on platelet respiration and its changes during the remission phases of disease, respectively.

โ€ข Bioblast editor: Plangger M, Tindle-Solomon L โ€ข O2k-Network Lab: RO Timisoara Muntean DM

Labels: MiParea: Respiration  Pathology: Cancer 

Organism: Human  Tissue;cell: Platelet  Preparation: Permeabilized cells 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, NS, ROX  HRR: Oxygraph-2k 


Lelcu T(1), Bรฎnฤƒ AM(1), Avram VF(1), Aburel OM(1,*), Borza C(1,*), Arghirescu S(2), Muntean DM(1,*)
  1. Dept Functional Sciences-Pathophysiology, *Center Translational Research Systems Medicine, "Victor Babeศ™" Univ Medicine Pharmacy
  2. Dept Pediatrics - The 3rd Clinic Pediatrics, "Victor Babeศ™" Univ Medicine Pharmacy; Timiศ™oara, Romania. - lelcu.theia@umft.ro


Lelcu Figure1 MiP2019.jpg


  1. Petrus AT, Lighezan DL, Danila MD, Duicu OM, Sturza A, Muntean DM, Ionita I (2019) Assessment of platelets respiration as emerging biomarker of disease. Physiol Res 68:347-63.
  2. Doerrier C, Garcia-Souza LF, Krumschnabel G, Wohlfarter Y, Mรฉszรกros AT, Gnaiger E (2018) High-resolution fluorespirometry and OXPHOS protocols for human cells, permeabilized fibers from small biopsies of muscle and isolated mitochondria. Methods Mol Biol 1782:31-70.
  3. Baaten CCFMJ, Moenen FCJI, Henskens YMC, Swieringa F, Wetzels RJH, van Oerle R, Heijnen HFG, Ten Cate H, Holloway GP, Beckers EAM, Heemskerk JWM, van der Meijden PEJ (2018) Impaired mitochondrial activity explains platelet dysfunction in thrombocytopenic cancer patients undergoing chemotherapy. Haematologica 103:1557-67.
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