ArticleLeukemia2019
Inhibition of SYK or BTK augments venetoclax sensitivity in SHP1-negative/BCL-2-positive diffuse large B-cell lymphoma.
Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
16 citing papers in PubMed, 29 citations in OpenAlex.
- Novel PI3kδ inhibitor roginolisib synergizes with venetoclax in hematologic malignancies.Haematologica · 2025Article
- Molecular Subtypes and the Role of TP53 in Diffuse Large B-Cell Lymphoma and Richter Syndrome.Cancers · 2024Review
- BR vs. R‑miniCHOP in unfit patients with B‑cell non‑Hodgkin lymphoma: A randomized, two‑center, cohort study.Oncology letters · 2023Article
- Apatinib enhances chemosensitivity of ABT-199 in diffuse large B-cell lymphoma.Molecular oncology · 2022Article
- Altered pathways and targeted therapy in double hit lymphoma.Journal of hematology & oncology · 2022Review
- Review
- Programmed cell death, redox imbalance, and cancer therapeutics.Apoptosis : an international journal on programmed cell death · 2021Review
- Precursor B-ALL Cell Lines Differentially Respond to SYK Inhibition by Entospletinib.International journal of molecular sciences · 2021Article
- Therapeutic Targets in Chronic Lymphocytic Leukemia.Cancers · 2020Article
- Biomarkers and novel therapeutic approaches for diffuse large B-cell lymphoma in the era of precision medicine.Oncotarget · 2020Review
- Combination strategies to overcome resistance to the BCL2 inhibitor venetoclax in hematologic malignancies.Cancer cell international · 2020Review
- BDA-366, a putative Bcl-2 BH4 domain antagonist, induces apoptosis independently of Bcl-2 in a variety of cancer cell models.Cell death & disease · 2020Article
- Enhancing venetoclax activity in hematological malignancies.Expert opinion on investigational drugs · 2020Review
- Mechanisms of B Cell Receptor Activation and Responses to B Cell Receptor Inhibitors in B Cell Malignancies.Cancers · 2020Review
- Mining Drug-Target Associations in Cancer: Analysis of Gene Expression and Drug Activity Correlations.Biomolecules · 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
18 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The BCL-2 inhibitor venetoclax has only limited activity in DLBCL despite frequent BCL-2 overexpression. Since constitutive activation of the B cell receptor (BCR) pathway has been reported in both ABC and GCB DLBCL, we investigated whether targeting SYK or BTK will increase sensitivity of DLBCL cells to venetoclax. We report that pharmacological inhibition of SYK or BTK synergistically enhances venetoclax sensitivity in BCL-2-positive DLBCL cell lines with an activated BCR pathway in vitro and in a xenograft model in vivo, despite the only modest direct cytotoxic effect. We further show that these sensitizing effects are associated with inhibition of the downstream PI3K/AKT pathway and changes in the expression of MCL-1, BIM, and HRK. In addition, we show that BCR-dependent GCB DLBCL cells are characterized by deficiency of the phosphatase SHP1, a key negative regulator of the BCR pathway. Re-expression of SHP1 in GCB DBLCL cells reduces SYK, BLNK, and GSK3 phosphorylation and induces corresponding changes in MCL1, BIM, and HRK expression. Together, these findings suggest that SHP1 deficiency is responsible for the constitutive activation of the BCR pathway in GCB DLBCL and identify SHP1 and BCL-2 as potential predictive markers for response to treatment with a venetoclax/BCR inhibitor combination.
Indexed as
Identifiers
What OpenQuestion holds
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.