ArticleBlood2014
PKC-β as a therapeutic target in CLL: PKC inhibitor AEB071 demonstrates preclinical activity in CLL.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 53 citations in OpenAlex.
- Pan-cancer analysis reveals the oncogenic and immunomodulatory roles of PTGFRN across human cancers.Scientific reports · 2026Article
- CLL to Richter syndrome: Integrating network strategies with experiments elucidating disease drivers and personalized therapies.Science advances · 2025Article
- Impact of Protein Kinase C Activation and Monoclonal Antibodies on Immune Checkpoint Regulation and B Cell Function in Patients with Chronic Lymphocytic Leukemia.Biomedicines · 2025Article
- CD44: a cancer stem cell marker and therapeutic target in leukemia treatment.Frontiers in immunology · 2024Review
- PKCβ Facilitates Leukemogenesis in Chronic Lymphocytic Leukaemia by Promoting Constitutive BCR-Mediated Signalling.Cancers · 2022Article
- Protein Kinase C (PKC) Isozymes as Diagnostic and Prognostic Biomarkers and Therapeutic Targets for Cancer.Cancers · 2022Review
- Protein kinase C targeting of luminal (T-47D), luminal/HER2-positive (BT474), and triple negative (HCC1806) breast cancer cells in-vitro with AEB071 (Sotrastaurin) is efficient but mediated by subtype specific molecular effects.Archives of gynecology and obstetrics · 2022Article
- GSK3β is a critical, druggable component of the network regulating the active NOTCH1 protein and cell viability in CLL.Cell death & disease · 2022Article
- Receptor tyrosine kinases regulate signal transduction through a liquid-liquid phase separated state.Molecular cell · 2022Article
- Novel Agents in Chronic Lymphocytic Leukemia: New Combination Therapies and Strategies to Overcome Resistance.Cancers · 2021Review
- Genetic and Non-Genetic Mechanisms of Resistance to BCR Signaling Inhibitors in B Cell Malignancies.Frontiers in oncology · 2020Article
- Bone marrow niches in haematological malignancies.Nature reviews. Cancer · 2020Review
- Stromal cell protein kinase C-β inhibition enhances chemosensitivity in B cell malignancies and overcomes drug resistance.Science translational medicine · 2020Article
- The Role of Notch and Wnt Signaling in MSC Communication in Normal and Leukemic Bone Marrow Niche.Frontiers in cell and developmental biology · 2020Review
- Selective targeting of NAMPT by KPT-9274 in acute myeloid leukemia.Blood advances · 2019Article
- Management of patients with chronic lymphocytic leukemia at high risk of relapse on ibrutinib therapy.Leukemia & lymphoma · 2018Review
- Notch2 controls non-autonomous Wnt-signalling in chronic lymphocytic leukaemia.Nature communications · 2018Article
- Inflammation and NF-κB Signaling in Prostate Cancer: Mechanisms and Clinical Implications.Cells · 2018Review
- Review
- Recent therapeutic advances in chronic lymphocytic leukemia.F1000Research · 2017Review
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 3 institutions in 2 countries.
Funding
Abstract
Targeting B-cell receptor (BCR) signaling in chronic lymphocytic leukemia (CLL) has been successful with durable remissions observed with several targeted therapeutics. Protein kinase C-β (PKC-β) is immediately downstream of BCR and has been shown to be essential to CLL cell survival and proliferation in vivo. We therefore evaluated sotrastaurin (AEB071), an orally administered potent PKC inhibitor, on CLL cell survival both in vitro and in vivo. AEB071 shows selective cytotoxicity against B-CLL cells in a dose-dependent manner. Additionally, AEB071 attenuates BCR-mediated survival pathways, inhibits CpG-induced survival and proliferation of CLL cells in vitro, and effectively blocks microenvironment-mediated survival signaling pathways in primary CLL cells. Furthermore, AEB071 alters β-catenin expression, resulting in decreased downstream transcriptional genes as c-Myc, Cyclin D1, and CD44. Lastly, our preliminary in vivo studies indicate beneficial antitumor properties of AEB071 in CLL. Taken together, our results indicate that targeting PKC-β has the potential to disrupt signaling from the microenvironment contributing to CLL cell survival and potentially drug resistance. Future efforts targeting PKC with the PKC inhibitor AEB071 as monotherapy in clinical trials of relapsed and refractory CLL patients are warranted.
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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.