ArticleLeukemia2022
Synergistic activity of combined inhibition of anti-apoptotic molecules in B-cell precursor ALL.
Article in Leukemia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 20 citations in OpenAlex.
- Metabolic vulnerabilities and therapeutic opportunities in diffuse large B-cell lymphoma.Oncogenesis · 2026Review
- Targeting signaling pathways in lymphoma: From molecular mechanisms to clinical breakthroughs.Chinese medical journal · 2026Review
- Therapeutic potential of BH3-mimetics and NK cell-mediated immunotherapy in T-ALL.Cell death & disease · 2026Article
- B-Cell Lymphoma 2 Inhibition in Acute Lymphoblastic Leukemia: Mechanisms, Resistance, and Emerging Combinations With Venetoclax.Journal of hematology · 2025Review
- Remission induction in refractory, drug resistant pediatric PICALM::MLLT10+ B-cell acute lymphoblastic leukemia by venetoclax.Leukemia · 2025Article
- Unveiling the potential of marine peptides in leukemia: mechanistic insights and future horizon in peptide research.Turkish journal of medical sciences · 2025Review
- The dual BCL-2 and BCL-XL inhibitor AZD4320 acts on-target and synergizes with MCL-1 inhibition in B-cell precursor ALL.Blood advances · 2024Article
- Venetoclax resistance in acute lymphoblastic leukemia is characterized by increased mitochondrial activity and can be overcome by co-targeting oxidative phosphorylation.Cell death & disease · 2024Article
- Combination p53 activation and BCL-xLeukemia · 2024Article
- Venetoclax and dinaciclib elicit synergistic preclinical efficacy against hypodiploid acute lymphoblastic leukemia.Haematologica · 2023Article
- Venetoclax Drug Increases the Apoptosis of T and B Acute Lymphoblastic Leukemia Cells by Reducing the Expression ofInternational journal of molecular and cellular medicine · 2023Article
- Current Status of Novel Agents for the Treatment of B Cell Malignancies: What's Coming Next?Cancers · 2022Review
- Rationale for Combining the BCL2 Inhibitor Venetoclax with the PI3K Inhibitor Bimiralisib in the Treatment of IDH2- and FLT3-Mutated Acute Myeloid Leukemia.International journal of molecular sciences · 2022Article
- Synergism of BCL-2 family inhibitors facilitates selective elimination of senescent cells.Aging · 2022Article
- Targeting Apoptosis in ALL.Current hematologic malignancy reports · 2022Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeting BCL-2, a key regulator of survival in B-cell malignancies including precursor B-cell acute lymphoblastic leukemia, has become a promising treatment strategy. However, given the redundancy of anti-apoptotic BCL-2 family proteins (BCL-2, BCL-XL, MCL-1), single targeting may not be sufficient. When analyzing the effects of BH3-mimetics selectively targeting BCL-XL and MCL-1 alone or in combination with the BCL-2 inhibitor venetoclax, heterogeneous sensitivity to either of these inhibitors was found in ALL cell lines and in patient-derived xenografts. Interestingly, some venetoclax-resistant leukemias were sensitive to the MCL-1-selective antagonist S63845 and/or BCL-XL-selective A-1331852 suggesting functional mutual substitution. Consequently, co-inhibition of BCL-2 and MCL-1 or BCL-XL resulted in synergistic apoptosis induction. Functional analysis by BH3-profiling and analysis of protein complexes revealed that venetoclax-treated ALL cells are dependent on MCL-1 and BCL-XL, indicating that MCL-1 or BCL-XL provide an Achilles heel in BCL-2-inhibited cells. The effect of combining BCL-2 and MCL-1 inhibition by venetoclax and S63845 was evaluated in vivo and strongly enhanced anti-leukemia activity was found in a pre-clinical patient-derived xenograft model. Our study offers in-depth molecular analysis of mutual substitution of BCL-2 family proteins in acute lymphoblastic leukemia and provides targets for combination treatment in vivo and in ongoing clinical studies.
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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.