ArticleNature communications2023
ABCC1 and glutathione metabolism limit the efficacy of BCL-2 inhibitors in acute myeloid leukemia.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
- DNA Methylation of Pharmacologic and Leukemia-Related Genes Predicts Clinical Outcomes in Pediatric Acute Myeloid Leukemia.Cancers · 2026Article
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- Resistance to Targeted Therapy in AML: Current Challenges and Emerging Treatment Strategies.Journal of clinical medicine · 2026Review
- Single cell Raman spectroscopic profiles predict treatment responses in patients withFrontiers in cell and developmental biology · 2026Article
- A Holistic Review of Oncological Drug Targets and Trajectories of Resistance in Cancer Therapy.Oncology research · 2026Review
- Cannabinoids in hematologic malignancies: mechanisms and therapeutic potential for overcoming drug resistance.Frontiers in pharmacology · 2026Review
- Functional heterogeneity of TP53 mutants in venetoclax-resistant AML: mechanisms, clinical implications, and therapeutic opportunities.Frontiers in oncology · 2026Review
- Venetoclax resistance in preclinical KMT2A-rearranged acute lymphoblastic leukemia models is characterized by high inter- and intra-model heterogeneity.NPJ precision oncology · 2025Article
- Genes-first and phenotypes-first paths to treatment resistance in hematological malignancies.Cell death & disease · 2025Review
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
- Understanding and overcoming multidrug resistance in cancer.Nature reviews. Clinical oncology · 2025Review
- Diverse Biological Processes Contribute to Transforming Growth Factor β-Mediated Cancer Drug Resistance.Cells · 2025Review
- An Isoform-Specific RUNX1C-BTG2 Axis Governs AML Quiescence and Chemoresistance.Blood cancer discovery · 2025Article
- Review
- Sitravatinib combined with venetoclax exerts effective synergy to eliminate acute myeloid leukemia cells with FLT3-ITD mutations.Translational oncology · 2025Article
- Design and in vitro evaluation of novel tetrazole derivatives of dianisidine as anticancer agents targeting Bcl-2 apoptosis regulator.Scientific reports · 2025Article
- C1GALT1 expression predicts poor survival in osteosarcoma and is crucial for ABCC1 transporter-mediated doxorubicin resistance.The Journal of pathology · 2025Article
- Integrative single-cell RNA sequencing and bulk RNA sequencing reveals the characteristics of glutathione metabolism and protective role of GSTA4 gene in pancreatic cancer.Frontiers in immunology · 2025Article
- Factors affecting response and resistance to venetoclax in acute myeloid leukemia.Frontiers in oncology · 2025Review
- LAPTM5 Confers the Resistance to Venetoclax via Promoting the Autophagosome-Lysosome Fusion in Multiple Myeloma.Journal of cellular and molecular medicine · 2025Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
Abstract
The BCL-2 inhibitor Venetoclax is a promising agent for the treatment of acute myeloid leukemia (AML). However, many patients are refractory to Venetoclax, and resistance develops quickly. ATP-binding cassette (ABC) transporters mediate chemotherapy resistance but their role in modulating the activity of targeted small-molecule inhibitors is unclear. Using CRISPR/Cas9 screening, we find that loss of ABCC1 strongly increases the sensitivity of AML cells to Venetoclax. Genetic and pharmacologic ABCC1 inactivation potentiates the anti-leukemic effects of BCL-2 inhibitors and efficiently re-sensitizes Venetoclax-resistant leukemia cells. Conversely, ABCC1 overexpression induces resistance to BCL-2 inhibitors by reducing intracellular drug levels, and high ABCC1 levels predicts poor response to Venetoclax therapy in patients. Consistent with ABCC1-specific export of glutathionylated substrates, inhibition of glutathione metabolism increases the potency of BCL-2 inhibitors. These results identify ABCC1 and glutathione metabolism as mechanisms limiting efficacy of BCL-2 inhibitors, which may pave the way to development of more effective therapies.
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Registered trials
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.