ArticleBlood2015
Inhibition of Mcl-1 with the pan-Bcl-2 family inhibitor (-)BI97D6 overcomes ABT-737 resistance in acute myeloid leukemia.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 140 citations in OpenAlex.
- Phase 2 study of chidamide in combination with CAG and venetoclax-azacitidine in older patients with newly diagnosed acute myeloid leukemia.Frontiers in immunology · 2025Trial
- 6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150).Blood cancer journal · 2021Trial
- Review
- Enitociclib (VIP152), venetoclax and prednisone in relapsed or refractory aggressive non-Hodgkin lymphoma.British journal of haematology · 2026Article
- NVP-2, in combination with Orlistat, represents a promising therapeutic strategy for acute myeloid leukemia.Cancer biology & therapy · 2025Article
- The Role of Senolytics in Osteoporosis.Biomolecules · 2025Review
- Characterization of stem cell landscape and assessing the stemness degree to aid clinical therapeutics in hematologic malignancies.Scientific reports · 2024Article
- STIM2 is involved in the regulation of apoptosis and the cell cycle in normal and malignant monocytic cells.Molecular oncology · 2024Article
- Ubiquitin-specific protease 7 inhibitors reveal a differentiated mechanism of p53-driven anti-cancer activity.iScience · 2024Article
- Distinct roles of hematopoietic cytokines in the regulation of leukemia stem cells in murine MLL-AF9 leukemia.Stem cell reports · 2024Article
- Moschus ameliorates glutamate-induced cellular damage by regulating autophagy and apoptosis pathway.Scientific reports · 2023Article
- ABCC1 and glutathione metabolism limit the efficacy of BCL-2 inhibitors in acute myeloid leukemia.Nature communications · 2023Article
- Dual targeting of BCL-2 and MCL-1 in the presence of BAX breaks venetoclax resistance in human small cell lung cancer.British journal of cancer · 2023Article
- Selective inhibition of MCL1 overcomes venetoclax resistance in a murine model of myelodysplastic syndromes.Haematologica · 2023Article
- Synergistic activity of ABT-263 and ONC201/TIC10 against solid tumor cell lines is associated with suppression of anti-apoptotic Mcl-1, BAG3, pAkt, and upregulation of pro-apoptotic Noxa and Bax cleavage during apoptosis.American journal of cancer research · 2023Article
- Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets.Journal of hematology & oncology · 2022Review
- AXL/MERTK inhibitor ONO-7475 potently synergizes with venetoclax and overcomes venetoclax resistance to killHaematologica · 2022Article
- Synergistic apoptotic effect of Mcl-1 inhibition and doxorubicin on B-cell precursor acute lymphoblastic leukemia cells.Molecular biology reports · 2022Article
- High expression of B4GALT1 is associated with poor prognosis in acute myeloid leukemia.Frontiers in genetics · 2022Article
- The Growing Role of the BH3 Mimetic Drug Venetoclax in the Therapy of Acute Myeloid Leukemia.Mediterranean journal of hematology and infectious diseases · 2022Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Overexpression of antiapoptotic Bcl-2 proteins such as Bcl-2, Bcl-xL, and Mcl-1 is widely associated with tumor initiation, progression, and chemoresistance. Furthermore, it has been demonstrated that Mcl-1 upregulation renders several types of cancers resistant to the Bcl-2/Bcl-xL inhibitors ABT-737 and ABT-263. The emerging importance of Mcl-1 in pathogenesis and drug resistance makes it a high-priority therapeutic target. In this study, we showed that inhibition of Mcl-1 with a novel pan-Bcl-2 inhibitor (-)BI97D6 potently induced apoptosis in acute myeloid leukemia (AML) cells. (-)BI97D6 induced hallmarks of mitochondrial apoptosis, disrupted Mcl-1/Bim and Bcl-2/Bax interactions, and stimulated cell death via the Bak/Bax-dependent mitochondrial apoptosis pathway, suggesting on-target mechanisms. As a single agent, this pan-Bcl-2 inhibitor effectively overcame AML cell apoptosis resistance mediated by Mcl-1 or by interactions with bone marrow mesenchymal stromal cells. (-)BI97D6 was also potent in killing refractory primary AML cells. Importantly, (-)BI97D6 killed AML leukemia stem/progenitor cells while largely sparing normal hematopoietic stem/progenitor cells. These findings demonstrate that pan-Bcl-2 inhibition by an Mcl-1-targeting inhibitor not only overcomes intrinsic drug resistance ensuing from functional redundancy of Bcl-2 proteins, but also abrogates extrinsic resistance caused by the protective tumor microenvironment.
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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.