Number of the records: 1  

Metabolic profile of leukemia cells influences treatment efficacy of L-asparaginase

  1. 1.
    0531282 - FGÚ 2021 RIV GB eng J - Journal Article
    Hložková, K. - Pecinová, Alena - Alquezar-Artieda, N. - Pajuelo-Reguera, D. - Šimčíková, M. - Hovorková, L. - Rejlová, K. - Žaliová, M. - Mráček, Tomáš - Kolenová, A. - Starý, J. - Trka, J. - Stárková, J.
    Metabolic profile of leukemia cells influences treatment efficacy of L-asparaginase.
    Bmc Cancer. Roč. 20, č. 1 (2020), č. článku 526. E-ISSN 1471-2407
    R&D Projects: GA ČR(CZ) GA16-12726S
    Institutional support: RVO:67985823
    Keywords : cancer metabolism * L-asparaginase * leukemia * resistance * glycolysis * mitochondrial respiration * fatty acid oxidation * mitochondrial membrane potential
    OECD category: Oncology
    Impact factor: 4.430, year: 2020
    Method of publishing: Open access
    https://bmccancer.biomedcentral.com/articles/10.1186/s12885-020-07020-y

    Effectiveness of L-asparaginase administration in acute lymphoblastic leukemia treatment is mirrored in the overall outcome of patients. Generally, leukemia patients differ in their sensitivity to L-asparaginase, however, the mechanism underlying their inter-individual differences is still not fully understood. We have previously shown that L-asparaginase rewires the biosynthetic and bioenergetic pathways of leukemia cells to activate both anti-leukemic and pro-survival processes. Herein, we investigated the relationship between the metabolic profile of leukemia cells and their sensitivity to currently used cytostatic drugs.MethodsAltogether, 19 leukemia cell lines, primary leukemia cells from 26 patients and 2 healthy controls were used. Glycolytic function and mitochondrial respiration were measured using Seahorse Bioanalyzer. Sensitivity to cytostatics was measured using MTS assay and/or absolute count and flow cytometry. Mitochondrial membrane potential was determined as TMRE fluorescence.Using cell lines and primary patient samples we characterized the basal metabolic state of cells derived from different leukemia subtypes and assessed their sensitivity to cytostatic drugs. We found that leukemia cells cluster into distinct groups according to their metabolic profile. Lymphoid leukemia cell lines and patients sensitive to L-asparaginase clustered into the low glycolytic cluster. While lymphoid leukemia cells with lower sensitivity to L-asparaginase together with resistant normal mononuclear blood cells gathered into the high glycolytic cluster. Furthermore, we observed a correlation of specific metabolic parameters with the sensitivity to L-asparaginase. Greater ATP-linked respiration and lower basal mitochondrial membrane potential in cells significantly correlated with higher sensitivity to L-asparaginase. No such correlation was found in the other cytostatic drugs tested by us.These data support that cell metabolism plays a prominent role in the treatment effect of L-asparaginase. Based on these findings, leukemia patients with lower sensitivity to L-asparaginase with no specific genetic characterization could be identified by their metabolic profile.
    Permanent Link: http://hdl.handle.net/11104/0309970

     
     
Number of the records: 1  

  This site uses cookies to make them easier to browse. Learn more about how we use cookies.