Evidence map›Paper›PMID 32503472›Full record

ArticleBMC cancer2020

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

Katerina Hlozkova, Alena Pecinova, Natividad Alquezar-Artieda, David Pajuelo-Reguera, Marketa Simcikova, Lenka Hovorkova, Katerina Rejlova, Marketa Zaliova, Tomas Mracek, Alexandra Kolenova and 3 more

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.2field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Secretory Expression ofJournal of microbiology and biotechnology · 2025
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  3. Molecular Reactivity in Maternal Pregnancy Blood and Neonatal Dried Blood Spots Is Associated with the Risk of Pediatric Acute Lymphoblastic Leukemia.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025
    Article
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  17. Antioxidants (Basel, Switzerland) · 2021
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 2 countries.

Katerina HlozkovaCLIP - Childhood Leukaemia Investigation Prague, Prague, Czech Republic.
Alena PecinovaDepartment of Bioenergetics, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
Natividad Alquezar-ArtiedaCLIP - Childhood Leukaemia Investigation Prague, Prague, Czech Republic.
David Pajuelo-RegueraCLIP - Childhood Leukaemia Investigation Prague, Prague, Czech Republic.
Marketa SimcikovaCLIP - Childhood Leukaemia Investigation Prague, Prague, Czech Republic.
Lenka HovorkovaCLIP - Childhood Leukaemia Investigation Prague, Prague, Czech Republic.
Katerina RejlovaCLIP - Childhood Leukaemia Investigation Prague, Prague, Czech Republic.
Marketa ZaliovaCLIP - Childhood Leukaemia Investigation Prague, Prague, Czech Republic.
Tomas MracekDepartment of Bioenergetics, Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
Alexandra KolenovaDepartment of Pediatric Hematology and Oncology, National Institute of Children's Diseases and Medical Faculty, Comenius University, Bratislava, Slovakia.
Jan StaryDepartment of Pediatric Hematology and Oncology, Second Faculty of Medicine, Charles University, Prague, Czech Republic.
Jan TrkaCLIP - Childhood Leukaemia Investigation Prague, Prague, Czech Republic.
Julia StarkovaCLIP - Childhood Leukaemia Investigation Prague, Prague, Czech Republic. julia.starkova@lfmotol.cuni.cz.
Charles University · CZComenius University Bratislava · SKCzech Academy of Sciences · CZCzech Academy of Sciences, Institute of Physiology · CZUniversity Hospital in Motol · CZ

Funding

Grantová Agentura České Republiky 16-12726SMinisterstvo Zdravotnictví Ceské Republiky NV18-07-00129
6 · The paper itself

Abstract

backgroundEffectiveness 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.

resultsUsing 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.

conclusionsThese 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.

Indexed as

AdolescentAntineoplastic AgentsAsparaginaseBiosynthetic PathwaysBone MarrowCell Line, TumorChildChild, PreschoolDrug Resistance, NeoplasmFemaleGlycolysisHumansInfantMaleMembrane Potential, MitochondrialMetabolomeAntineoplastic AgentsAsparaginasecancer metabolismfatty acid oxidationglycolysisL-asparaginaseleukemiamitochondrial membrane potentialmitochondrial respirationresistance

Identifiers

PMID32503472
PMCPMC7275298
OpenAlexW3032956551

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.