ArticleCancer research2015
BH3 Inhibitor Sensitivity and Bcl-2 Dependence in Primary Acute Lymphoblastic Leukemia Cells.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 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
66 citing papers in PubMed, 136 citations in OpenAlex.
- A phase 1/2 study of mini-hyper-CVD plus venetoclax in patients with relapsed/refractory acute lymphoblastic leukemia.Blood advances · 2024Trial
- An Open-label, Phase II Trial of Entospletinib (GS-9973), a Selective Spleen Tyrosine Kinase Inhibitor, in Diffuse Large B-cell Lymphoma.Clinical lymphoma, myeloma & leukemia · 2018Trial
- Differential mitochondrial priming by BCR::ABL1 in B-cell precursor acute lymphoblastic leukemia.Leukemia · 2026Article
- Therapeutic potential of BH3-mimetics and NK cell-mediated immunotherapy in T-ALL.Cell death & disease · 2026Article
- Mini-hyper-CVD plus venetoclax and navitoclax for relapsed/refractory acute lymphoblastic leukemia.Blood advances · 2026Article
- The use of venetoclax in the treatment of acute lymphoblastic leukemia-a systematic review.Therapeutic advances in medical oncology · 2026Review
- Review
- Decoding the diagnostic biomarkers of mitochondrial dysfunction related gene variants in pediatric T cell acute lymphoblastic leukemia.Scientific reports · 2025Article
- Review
- Venetoclax plus low-intensity chemotherapy for adults with acute lymphoblastic leukemia.Blood advances · 2025Article
- 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 leads to broad resistance to standard-of-care anti-MM agents, but not to immunotherapies.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
- Low expression of miR-182 caused by DNA hypermethylation accelerates acute lymphocyte leukemia development by targeting PBX3 and BCL2: miR-182 promoter methylation is a predictive marker for hypomethylation agents + BCL2 inhibitor venetoclax.Clinical epigenetics · 2024Article
- Nelarabine: when and how to use in the treatment of T-cell acute lymphoblastic leukemia.Blood advances · 2024Review
- BH3 profiling identifies BCL-2 dependence in adult patients with early T-cell progenitor acute lymphoblastic leukemia.Blood advances · 2023Article
- Venetoclax Use in Paediatric Haemato-Oncology Centres in Poland: A 2022 Survey.Children (Basel, Switzerland) · 2023Article
- Nelarabine combination therapy for relapsed or refractory T-cell acute lymphoblastic lymphoma/leukemia.Blood advances · 2023Article
- Venetoclax Penetrates the Blood Brain Barrier: A Pharmacokinetic Analysis in Pediatric Leukemia Patients.Journal of Cancer · 2023Article
- Post-Hematopoietic Cell Transplantation Relapsed Acute Lymphoblastic Leukemia: Current Challenges and Future Directions.OncoTargets and therapy · 2023Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
BH3 mimetic drugs may be useful to treat acute lymphoblastic leukemia (ALL) but the sensitivity of primary tumor cells has not been fully evaluated. Here, B-lineage ALL cell cultures derived from a set of primary tumors were studied with respect to sensitivity to the BH3 mimetics ABT-263 and ABT-199 and to Bcl-2 dependence and function. These ALL cells each expressed high levels of Bcl-2 and exhibited great sensitivity to ABT-263 and ABT-199, which induced rapid apoptotic cell death. BH3 profiling indicated that the ALL cultures were Bcl-2 dependent. Coimmunoprecipitation studies revealed a multifaceted role for Bcl-2 in binding proapoptotic partners including Bax, Bak, Bik, and Bim. ABT-263 disrupted Bcl-2:Bim interaction in cells. Mcl-1 overexpression rendered ALL cells resistant to ABT-263 and ABT-199, with Mcl-1 assuming the role of Bcl-2 in binding Bim. Freshly isolated pediatric ALL blasts also expressed high levels of Bcl-2 and exhibited high sensitivity to Bcl-2 inhibition by the BH3 mimetic compounds. Overall, our results showed that primary ALL cultures were both more sensitive to BH3 mimetics and more uniform in their response than established ALL cell lines that have been evaluated previously. Furthermore, the primary cell model characterized here offers a powerful system for preclinical testing of novel drugs and drug combinations to treat ALL.
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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.