ArticleCancers2020
Cotargeting of Mitochondrial Complex I and Bcl-2 Shows Antileukemic Activity against Acute Myeloid Leukemia Cells Reliant on Oxidative Phosphorylation.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 44 citations in OpenAlex.
- Mitochondrial integrated stress response activation creates a therapeutic vulnerability to MCL-1 inhibition in acute myeloid leukemia.Cell death & disease · 2026Article
- Exploring the Bone Marrow Microenvironment as a Therapeutic Barrier and Targetable Source of Crosstalk in Acute Myeloid Leukemia.Blood and lymphatic cancer : targets and therapy · 2026Review
- Mitochondrial metabolism in cancer stem cells (CSCs): molecular and diagnostic implications.Frontiers in molecular biosciences · 2026Review
- The tumor microenvironment in leukemia: molecular pathways of immune evasion.Frontiers in immunology · 2026Review
- A TROP2-targeting ADC synergizes with oxidative phosphorylation inhibitor to enhance apoptosis in ESCC by suppressing the PI3K-AKT-mTOR signaling pathway.Cell death & disease · 2025Article
- Pitavastatin counteracts venetoclax resistance mechanisms in acute myeloid leukemia by depleting geranylgeranyl pyrophosphate.bioRxiv : the preprint server for biology · 2025Article
- Apoptosis-targeting BH3 mimetics: transforming treatment for patients with acute myeloid leukaemia.Nature reviews. Clinical oncology · 2025Review
- Acute myeloid leukemia mitochondria hydrolyze ATP to support oxidative metabolism and resist chemotherapy.Science advances · 2025Article
- Targeting cancer and immune cell metabolism with the complex I inhibitors metformin and IACS-010759.Molecular oncology · 2024Review
- The Imipridone ONC213 Targets α-Ketoglutarate Dehydrogenase to Induce Mitochondrial Stress and Suppress Oxidative Phosphorylation in Acute Myeloid Leukemia.Cancer research · 2024Article
- Chronic lymphocytic leukemia patient-derived xenografts recapitulate clonal evolution to Richter transformation.Leukemia · 2024Article
- Enhancing anti-AML activity of venetoclax by isoflavone ME-344 through suppression of OXPHOS and/or purine biosynthesis in vitro.Biochemical pharmacology · 2024Article
- Electron transport chain and mTOR inhibition synergistically decrease CD40 signaling and counteract venetoclax resistance in chronic lymphocytic leukemia.Haematologica · 2024Article
- A New Quinone-Based Inhibitor of Mitochondrial Complex I in D-Conformation, Producing Invasion Reduction and Sensitization to Venetoclax in Breast Cancer Cells.Antioxidants (Basel, Switzerland) · 2023Article
- ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/β-catenin signaling by palmitoylation modification.Frontiers of medicine · 2023Article
- PTMA binds to HMGB1 to regulate mitochondrial oxidative phosphorylation and thus affect the malignant progression of esophageal squamous cell carcinoma.Journal of thoracic disease · 2023Article
- Targeting chemoresistance and mitochondria-dependent metabolic reprogramming in acute myeloid leukemia.Frontiers in oncology · 2023Review
- Co-targeting of HDAC, PI3K, and Bcl-2 results in metabolic and transcriptional reprogramming and decreased mitochondrial function in acute myeloid leukemia.Biochemical pharmacology · 2022Article
- Intrinsic adaptations in OXPHOS power output and reduced tumorigenicity characterize doxorubicin resistant ovarian cancer cells.Biochimica et biophysica acta. Bioenergetics · 2022Article
- Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
Targeting oxidative phosphorylation (OXPHOS) is a promising strategy to improve treatment outcomes of acute myeloid leukemia (AML) patients. IACS-010759 is a mitochondrial complex I inhibitor that has demonstrated preclinical antileukemic activity and is being tested in Phase I clinical trials. However, complex I deficiency has been reported to inhibit apoptotic cell death through prevention of cytochrome c release. Thus, combining IACS-010759 with a BH3 mimetic may overcome this mechanism of resistance leading to synergistic antileukemic activity against AML. In this study, we show that IACS-010759 and venetoclax synergistically induce apoptosis in OXPHOS-reliant AML cell lines and primary patient samples and cooperatively target leukemia progenitor cells. In a relatively OXPHOS-reliant AML cell line derived xenograft mouse model, IACS-010759 treatment significantly prolonged survival, which was further enhanced by treatment with IACS-010759 in combination with venetoclax. Consistent with our hypothesis, IACS-010759 treatment indeed retained cytochrome c in mitochondria, which was completely abolished by venetoclax, resulting in Bak/Bax- and caspase-dependent apoptosis. Our preclinical data provide a rationale for further development of the combination of IACS-010759 and venetoclax for the treatment of patients with AML.
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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.