ArticleBiochemical pharmacology2022
Co-targeting of HDAC, PI3K, and Bcl-2 results in metabolic and transcriptional reprogramming and decreased mitochondrial function in acute myeloid leukemia.
Article in Biochemical pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Histone deacetylases in cancer metabolic reprogramming.Experimental & molecular medicine · 2026Review
- PI3Kδ inhibitor YY‑20394 is effective alone or in combination with Bcl‑2 inhibitor ABT199 in acute myeloid leukemia cells.Oncology reports · 2026Article
- MO-IPS suppresses acute myeloid leukemia through metabolic reprogramming and synergizes with anti-PD-1 immunotherapy.Functional & integrative genomics · 2026Article
- Activation of c-Myc confers resistance to venetoclax via inhibition of Bim in t(8;21)-positive acute myeloid leukemia.Cell communication and signaling : CCS · 2026Article
- Loss of cystathionine-β-synthase contributes to elevated OXPHOS, a vulnerability in Ara-C-resistant Myeloid Leukemia in Down syndrome.Biochemical pharmacology · 2026Article
- Inhibition of CDK9 enhances AML cell death induced by combined venetoclax and azacitidine.Molecular oncology · 2026Article
- Unraveling Venetoclax Resistance: Navigating the Future of HMA/Venetoclax-Refractory AML in the Molecular Era.Cancers · 2025Review
- Dual PI3K and HDAC inhibitor, CUDC-907, effectively inhibits endometrial cancer growthFrontiers in oncology · 2025Article
- Targeting ribonucleotide reductase to enhance the antileukemic activity of gilteritinib against chemoresistantASPET discovery · 2025Article
- Panobinostat sensitizes AraC-resistant AML cells to the combination of azacitidine and venetoclax.Biochemical pharmacology · 2024Article
- Review
- The Imipridone ONC213 Targets α-Ketoglutarate Dehydrogenase to Induce Mitochondrial Stress and Suppress Oxidative Phosphorylation in Acute Myeloid Leukemia.Cancer research · 2024Article
- Venetoclax Resistance in Acute Myeloid Leukemia.Cancers · 2024Review
- Venetoclax efficacy on acute myeloid leukemia is enhanced by the combination with butyrate.Scientific reports · 2024Article
- Synergistic effect of adavosertib and fimepinostat on acute myeloid leukemia cells by enhancing the induction of DNA damage.Investigational new drugs · 2024Article
- Enhancing anti-AML activity of venetoclax by isoflavone ME-344 through suppression of OXPHOS and/or purine biosynthesis in vitro.Biochemical pharmacology · 2024Article
- BCL-2 inhibitors in hematological malignancies: biomarkers that predict response and management strategies.Frontiers in oncology · 2024Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Despite the recently approved new therapies, the clinical outcomes of acute myeloid leukemia (AML) patients remain disappointing, highlighting the need for novel therapies. Our lab has previously demonstrated the promising outlook for CUDC-907, a dual inhibitor of PI3K and HDAC, in combination with venetoclax (VEN), against AML both in vitro and in vivo at least partially through suppression of c-Myc. In this study, we further elucidated the mechanism of action of the combination in preclinical models of AML. We demonstrated that the combination significantly reduced primary AML cell engraftment in immunocompromised mice. RNA sequencing and metabolomics analyses revealed that the combination reduced the levels for mRNAs of key TCA cycle genes and metabolites in the TCA cycle, respectively. This was accompanied by a reduced oxygen consumption rate (OCR), demonstrating that the combination suppressed oxidative phosphorylation (OXPHOS). Metabolomics analyses revealed that a large number of metabolites upregulated in AraC-resistant AML cells could be downregulated by the combination. CUDC-907 synergized with VEN in inducing apoptosis in the AraC-resistant AML cells. In conclusion, the CUDC-907 and VEN combination induces metabolic and transcriptomic reprograming and suppression of OXPHOS in AML, which provides additional mechanisms underlying the synergy between the two agents.
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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.