ArticleEuropean journal of clinical pharmacology2012
Carbonyl reductase 1 expression influences daunorubicin metabolism in acute myeloid leukemia.
Article in European journal of clinical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 33 citations in OpenAlex.
- Integrated drug resistance and leukemic stemness gene-expression scores predict outcomes in large cohort of over 3500 AML patients from 10 trials.NPJ precision oncology · 2024Article
- A Novel Fatty Acid Metabolism-Associated Risk Model for Prognosis Prediction in Acute Myeloid Leukaemia.Current oncology (Toronto, Ont.) · 2023Article
- Construction and validation of a fatty acid metabolism risk signature for predicting prognosis in acute myeloid leukemia.BMC genomic data · 2022Article
- Daunorubicin and Its Active Metabolite Pharmacokinetic Profiles in Acute Myeloid Leukaemia Patients: A Pharmacokinetic Ancillary Study of the BIG-1 Trial.Pharmaceutics · 2022Article
- Five EMT-Related Gene Signatures Predict Acute Myeloid Leukemia Patient Outcome.Disease markers · 2022Article
- Selective inhibition of aldo-keto reductase 1C3: a novel mechanism involved in midostaurin and daunorubicin synergism.Archives of toxicology · 2021Article
- Olaparib Synergizes the Anticancer Activity of Daunorubicin via Interaction with AKR1C3.Cancers · 2020Article
- A personalized approach to acute myeloid leukemia therapy: current options.Pharmacogenomics and personalized medicine · 2019Article
- Association between CBR1 polymorphisms and NSCLC in the Chinese population.Oncology letters · 2017Article
- Metabolic carbonyl reduction of anthracyclines - role in cardiotoxicity and cancer resistance. Reducing enzymes as putative targets for novel cardioprotective and chemosensitizing agents.Investigational new drugs · 2017Review
- Population pharmacokinetics of Daunorubicin in adult patients with acute myeloid leukemia.Cancer chemotherapy and pharmacology · 2016Article
- Single nucleotide polymorphisms in ABCB1 and CBR1 can predict toxicity to R-CHOP type regimens in patients with diffuse non-Hodgkin lymphoma.Haematologica · 2015Article
- Role of Drug Metabolism in the Cytotoxicity and Clinical Efficacy of Anthracyclines.Current drug metabolism · 2015Review
- Impact of genetic polymorphisms on chemotherapy toxicity in childhood acute lymphoblastic leukemia.Frontiers in genetics · 2012Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe present study aimed to investigate the role of expression of daunorubicin-metabolizing enzymes carbonyl reductase 1 and 3 (CBR1 and CBR3) on the in vitro cytotoxicity of daunorubicin in primary acute myeloid leukemia (AML) cells and the effect of genetic variants in CBR1 and CBR3 on the plasma pharmacokinetics of daunorubicin and daunorubicinol (DOL) in AML patients.
methodsRNA expression of CBR1 and CBR3, intracellular daunorubicin and DOL levels, and in vitro cytotoxicity of daunorubicin were measured in bone marrow mononuclear cells of 104 adult AML patients. Plasma pharmacokinetics of daunorubicin and DOL was measured in 24 patients receiving daunorubicin-based induction chemotherapy for AML.
resultsIncreased expression of CBR1 significantly reduced the in vitro cytotoxicity of daunorubicin and also positively correlated with intracellular DOL levels. Polymorphisms in CBR1 and CBR3 did not show any association with intracellular daunorubicin or DOL levels, but there was a trend towards significant increase in plasma daunorubicin systemic exposure in patients with a variant genotype for CBR1 polymorphism rs25678.
conclusionsThis pilot study suggests that CBR1 RNA expression may be helpful in identifying AML patients at risk of developing resistance or toxicity to daunorubicin due to increased formation of DOL. Further confirmation of these findings in a larger sample pool would be required to determine the applicability of these results. Inhibition of CBR1 can be an option to improve the efficacy and prevent toxicity related to the treatment. Influence of daunorubicin and DOL plasma levels on clinical outcome, if any, remains to be evaluated.
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