ArticleOncotarget2015
Biological rational for sequential targeting of Bruton tyrosine kinase and Bcl-2 to overcome CD40-induced ABT-199 resistance in mantle cell lymphoma.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 79 citations in OpenAlex.
- Trial
- Impact of Venetoclax Exposure on Clinical Efficacy and Safety in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia.Clinical pharmacokinetics · 2017Trial
- Bendamustine switches TNF receptor superfamily signal from a survival to a death signal in B-cell lymphomas.Blood neoplasia · 2025Article
- [A preliminary analysis of the efficacy and safety of homoharringtonine, venetoclax, and azacitidine for newly diagnosed acute myeloid leukemia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Article
- Article
- Selective pharmacologic targeting of CTPS1 shows single-agent activity and synergizes with BCL2 inhibition in aggressive mantle cell lymphoma.Haematologica · 2024Article
- Venetoclax therapy and emerging resistance mechanisms in acute myeloid leukaemia.Cell death & disease · 2024Review
- Efficacy of coxsackievirus A21 against drug-resistant neoplastic B cells.Molecular therapy oncolytics · 2023Article
- Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax.Cancer discovery · 2023Article
- Inhibition of casein kinase 2 sensitizes mantle cell lymphoma to venetoclax through MCL-1 downregulation.Haematologica · 2023Article
- Effective tumor cell abrogation via Venetoclax-mediated BCL-2 inhibition in KMT2A-rearranged acute B-lymphoblastic leukemia.Cell death discovery · 2022Article
- Review
- Progress in understanding the mechanisms of resistance to BCL-2 inhibitors.Experimental hematology & oncology · 2022Review
- PIK-75 overcomes venetoclax resistanceAmerican journal of cancer research · 2022Article
- Novel Agents in Chronic Lymphocytic Leukemia: New Combination Therapies and Strategies to Overcome Resistance.Cancers · 2021Review
- BH3 Mimetics for the Treatment of B-Cell Malignancies-Insights and Lessons from the Clinic.Cancers · 2020Review
- Targeting BCL-2 in B-cell malignancies and overcoming therapeutic resistance.Cell death & disease · 2020Review
- Combination strategies to overcome resistance to the BCL2 inhibitor venetoclax in hematologic malignancies.Cancer cell international · 2020Review
- PI3Kδ inhibition reshapes follicular lymphoma-immune microenvironment cross talk and unleashes the activity of venetoclax.Blood advances · 2020Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aggressive biological behavior of mantle cell lymphoma (MCL) and its short response to current treatment highlight a great need for better rational therapy. Herein, we investigate the ability of ABT-199, the Bcl-2-selective BH3 mimetic, to kill MCL cells. Among MCL cell lines tested (n = 8), only three were sensitive (LD50 < 200 nM). In contrast, all primary MCL samples tested (n = 11) were highly sensitive to ABT-199 (LD50 < 10 nM). Mcl-1 and Bcl-xL both confer resistance to ABT-199-specific killing and BCL2/(BCLXL+MCL1) mRNA ratio is a strong predictor of sensitivity. By mimicking the microenvironment through CD40 stimulation, we show that ABT-199 sensitivity is impaired through activation of NF-kB pathway and Bcl-x(L) up-regulation. We further demonstrate that resistance is rapidly lost when MCL cells detach from CD40L-expressing fibroblasts. It has been reported that ibrutinib induces lymphocytosis in vivo holding off malignant cells from their protective microenvironment. We show here for two patients undergoing ibrutinib therapy that mobilized MCL cells are highly sensitive to ABT-199. These results provide evidence that in situ ABT-199 resistance can be overcome when MCL cells escape from the lymph nodes. Altogether, our data support the clinical application of ABT-199 therapy both as a single agent and in sequential combination with BTK inhibitors.
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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.