ArticleAmerican journal of translational research2016
Synergistic anti-leukemic interactions between ABT-199 and panobinostat in acute myeloid leukemia
Article in American journal of translational research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Enhancing venetoclax efficacy in leukemia through association with HDAC inhibitors.Cell death discovery · 2025Article
- Panobinostat sensitizes AraC-resistant AML cells to the combination of azacitidine and venetoclax.Biochemical pharmacology · 2024Article
- The Impact of Panobinostat on Cell Death in Combination with S63845 in Multiple Myeloma Cells.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2023Article
- Identification of a venetoclax-resistance prognostic signature base on 6-senescence genes and its clinical significance for acute myeloid leukemia.Frontiers in oncology · 2023Article
- Targeting replication stress in cancer therapy.Nature reviews. Drug discovery · 2023Review
- Synergistic efficacy of homoharringtonine and venetoclax on acute myeloid leukemia cells and the underlying mechanisms.Annals of translational medicine · 2022Article
- Venetoclax in Relapsed/Refractory Acute Myeloid Leukemia: Are Supporting Evidences Enough?Cancers · 2021Review
- Synergistic effect of chidamide and venetoclax on apoptosis in acute myeloid leukemia cells and its mechanism.Annals of translational medicine · 2021Article
- Targeting epigenetic mechanisms to overcome venetoclax resistance.Biochimica et biophysica acta. Molecular cell research · 2021Review
- Role of HDACs in normal and malignant hematopoiesis.Molecular cancer · 2020Review
- Venetoclax-Based Combinations in Acute Myeloid Leukemia: Current Evidence and Future Directions.Frontiers in oncology · 2020Review
- Venetoclax for AML: changing the treatment paradigm.Blood advances · 2019Article
- The Role of the BCL-2 Family of Proteins in HIV-1 Pathogenesis and Persistence.Clinical microbiology reviews · 2019Review
- HDAC Inhibitors in Acute Myeloid Leukemia.Cancers · 2019Review
- The Role of Inhibition of Apoptosis in Acute Leukemias and Myelodysplastic Syndrome.Frontiers in oncology · 2019Review
- Article
- A link between the fibroblast growth factor axis and the miR-16 family reveals potential new treatment combinations in mesothelioma.Molecular oncology · 2018Article
- Targeted therapy with a selective BCL-2 inhibitor in older patients with acute myeloid leukemia.Hematology, transfusion and cell therapyReview
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Cure rates for acute myeloid leukemia (AML) remain suboptimal; thus new treatment strategies are needed for this deadly disease. Poor clinical outcomes have been associated with overexpression of the anti-apoptotic Bcl-2 family proteins Bcl-2, Bcl-xL, and Mcl-1, which have garnered great interest as therapeutic targets. While the Bcl-2-selective inhibitor ABT-199 has demonstrated promising preclinical anti-leukemic activities, intrinsic drug resistance remains a problem. In our most recent study, we identified Mcl-1 sequestration of Bim as a mechanism of intrinsic resistance to ABT-199 in AML cells, thus upregulating Bim could overcome such resistance. Histone deacetylase (HDAC) inhibitors (HDACI) are a class of agents that have been confirmed to upregulate Bim. This prompted our hypothesis that combining an HDACI with ABT-199 would overcome intrinsic resistance to ABT-199 and result in synergistic anti-leukemic activity against AML. In this study, we investigated the anti-leukemic activity of panobinostat, a pan-HDACI, in combination with ABT-199 in AML cell lines and primary patient samples. We found that the combined drug treatment resulted in synergistic induction of cell death in both AML cell lines and primary patient samples. Panobinostat treatment resulted in upregulation of Bim, which remained elevated in the presence of ABT-199. In addition, shRNA knockdown of Bim in AML cell lines significantly attenuated apoptosis induced by combined panobinostat and ABT-199. Our results provide compelling evidence that Bim plays a key role in the combined anti-leukemic activity of panobinostat and ABT-199 against AML, and support clinical evaluation of combined panobinostat and ABT-199 in the treatment of AML.
Indexed as
Identifiers
27725868PMC5040686W2563332856What OpenQuestion holds
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.