ReviewInternational journal of molecular sciences2023
Venetoclax and Hypomethylating Agent Combination in Myeloid Malignancies: Mechanisms of Synergy and Challenges of Resistance.
Review in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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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.
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.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- Venetoclax for elderly patients with acute myeloid leukaemia unfit for intensive chemotherapy: Prospects, resistance mechanisms and management strategies.Clinical and translational medicine · 2026Review
- DNA methyltransferase inhibitors in oncology: clinical progress, limitations and future directions.Epigenomics · 2026Review
- Tinnitus severity and chronicity in relation to hearing loss: a population-based study.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026Article
- DNA methyltransferase inhibitors in hematological malignancies and solid tumors.International journal of cancer · 2026Review
- Using gene methylation detection in bronchoscopic samples combined with morphology-based pathology for lung cancer diagnosis.Frontiers in oncology · 2026Article
- Article
- Successful induction of remission with azacitidine, venetoclax, and dasatinib followed by allogeneic hematopoietic stem cell transplantation in a patient with Philadelphia chromosome-positive mixed phenotype acute leukemia (B/myeloid): a case report.Frontiers in medicine · 2026Article
- PML::RARα+ myeloid cells display metabolic alterations that can be targeted to treat resistant/relapse acute promyelocytic leukemias.Leukemia · 2025Article
- Does the Timing of Response Impact the Outcome of Relapsed/Refractory Acute Myeloid Leukemia Treated with Venetoclax in Combination with Hypomethylating Agents? A Proof of Concept from a Monocentric Observational Study.Journal of clinical medicine · 2025Article
- Exposing the DNA methylation-responsive compartment of the leukaemic genome in T-ALL cell lines support its potential as a novel therapeutic target in T-ALL.Clinical epigenetics · 2025Article
- The role of Bcl‑2 in controlling the transition between autophagy and apoptosis (Review).Molecular medicine reports · 2025Review
- The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy.Signal transduction and targeted therapy · 2025Review
- Recent advances in the role of atypical cadherin FAT1 in tumorigenesis (Review).Oncology letters · 2025Review
- Epigenetic mechanisms of drug resistance in acute myeloid leukemia: advances in small-molecule targeted therapy.Frontiers in pharmacology · 2025Review
- Targeting regulated cell death pathways in cancers for effective treatment: a comprehensive review.Frontiers in cell and developmental biology · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There has been a widespread adoption of hypomethylating agents (HMA: 5-Azacytidine (5-Aza)/decitabine) and venetoclax (Ven) for the treatment of acute myeloid leukemia (AML); however, the mechanisms behind the combination's synergy are poorly understood. Monotherapy often encounters resistance, leading to suboptimal outcomes; however, the combination of HMA and Ven has demonstrated substantial improvements in treatment responses. This study elucidates multiple synergistic pathways contributing to this enhanced therapeutic effect. Key mechanisms include HMA-mediated downregulation of anti-apoptotic proteins, notably MCL-1, and the priming of cells for Ven through the induction of genes encoding pro-apoptotic proteins such as Noxa. Moreover, Ven induces sensitization to HMA, induces overcoming resistance by inhibiting the DHODH enzyme, and disrupts antioxidant pathways (Nrf2) induced by HMA. The combination further disrupts oxidative phosphorylation in leukemia stem cells, amplifying the therapeutic impact. Remarkably, clinical studies have revealed a favorable response, particularly in patients harboring specific mutations, such as
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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.