ArticleOncotarget2018
Genetic biomarkers predict response to dual BCL-2 and MCL-1 targeting in acute myeloid leukaemia cells.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Venetoclax-Based Therapy for Early Relapse in Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report and Minireview.Cancer reports (Hoboken, N.J.) · 2026Review
- How to drug a leukemic stem cell: deciphering heterogeneity for better specificity.Blood neoplasia · 2025Review
- Multidrug Resistance: Are We Still Afraid of the Big Bad Wolf.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Venetoclax with decitabine or azacitidine in relapsed or refractory acute myeloid leukemia.Medical oncology (Northwood, London, England) · 2024Article
- Identification of bicyclic compounds that act as dual inhibitors of Bcl-2 and Mcl-1.Molecular diversity · 2023Article
- How ITD Insertion Sites Orchestrate the Biology and Disease of FLT3-ITD-Mutated Acute Myeloid Leukemia.Cancers · 2023Review
- Synergistic Action of MCL-1 Inhibitor with BCL-2/BCL-XL or MAPK Pathway Inhibitors Enhances Acute Myeloid Leukemia Cell Apoptosis and Differentiation.International journal of molecular sciences · 2023Article
- The manipulation of apoptosis for cancer therapy using BH3-mimetic drugs.Nature reviews. Cancer · 2022Review
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- Potential Biomarkers for Treatment Response to the BCL-2 Inhibitor Venetoclax: State of the Art and Future Directions.Cancers · 2021Review
- Tumor-targeted nanoparticles improve the therapeutic index of BCL2 and MCL1 dual inhibition.Blood · 2021Article
- Article
- Review
- Deciphering the Therapeutic Resistance in Acute Myeloid Leukemia.International journal of molecular sciences · 2020Review
- Synergistic effect of BCL2 and FLT3 co-inhibition in acute myeloid leukemia.Journal of hematology & oncology · 2020Article
- Multiple myeloma with 1q21 amplification is highly sensitive to MCL-1 targeting.Blood advances · 2019Article
- [Successful treatment with venetoclax and demethylation drugs in one acute myeloid leukemia patient relapsed after cord blood stem cell transplantation: a case report and literature review].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2019Review
- Imipridone ONC212 activates orphan G protein-coupled receptor GPR132 and integrated stress response in acute myeloid leukemia.Leukemia · 2019Article
- Venetoclax-based therapies for acute myeloid leukemia.Best practice & research. Clinical haematology · 2019Review
- Targeting sphingosine kinase 2 suppresses cell growth and synergizes with BCL2/BCL-XL inhibitors through NOXA-mediated MCL1 degradation in cholangiocarcinoma.American journal of cancer research · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukaemia (AML) cells often up-regulate pro-survival members of the BCL-2 protein family, such as BCL-2 and MCL-1, to avoid apoptosis. Venetoclax (ABT-199) targets BCL-2 and has shown promising efficacy in AML but over-expression of MCL-1 can cause resistance. A co-operative approach, targeting both BCL-2 and MCL-1 may therefore prove beneficial. This study investigated the potential synergistic relationship between Venetoclax and the MCL-1 inhibitor S63845 in AML cells. We treated MV4-11 cells and primary AML samples for 4 hours with Venetoclax, S63845 or the combination. We used a short-term flow cytometric technique to assess synergy using cytochrome C release as a read out of response. The combination of Venetoclax and S63845 produced a synergistic apoptotic response in MV4-11 cells and primary samples, including the leukaemia re-populating leukaemic stem cell (LSC) population, in 92% of the samples. Known molecular biomarkers of response to BCL-2 and MCL-1 targeting agents were corroborated, and augmented, with the short-term functional assay. The assay also predicted potential biomarkers of response to the combination of BCL-2 and MCL-1 targeting agents. Primary samples with an IDH2_140 mutation were more sensitive to Venetoclax as a single agent whereas samples with a FLT3-ITD mutation were more resistant. This resistance could be reversed when combined with S63845. All FLT3-ITD and NPM1 mutated samples were sensitive to the combination of drugs. We report that co-operatively targeting BCL-2 and MCL-1 may be beneficial in AML and a short-term
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