ArticleBlood2016
Targeting BTK through microRNA in chronic lymphocytic leukemia.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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
15 citing papers in PubMed, 32 citations in OpenAlex.
- HDAC1 regulates the chromatin landscape to control transcriptional dependencies in chronic lymphocytic leukemia.Blood advances · 2023Article
- Review
- Histone acetylation modification regulator-mediated tumor microenvironment infiltration characteristics and prognostic model of lung adenocarcinoma patients.Journal of thoracic disease · 2022Article
- The Role of Bruton's Kinase Inhibitors in Chronic Lymphocytic Leukemia: Current Status and Future Directions.Cancers · 2022Review
- Case Report: Dual Inhibition of HDAC and BTK for Diffuse Large B-Cell Lymphoma After Failure to CD19-Targeted CAR-T Therapy.Frontiers in immunology · 2022Article
- Bruton's Tyrosine Kinase Inhibition as an Emerging Therapy in Systemic Autoimmune Disease.Drugs · 2021Review
- Article
- Review
- MicroRNA-425 inhibits proliferation of chronic lymphocytic leukaemia cells through regulation of the Bruton's tyrosine kinase/phospholipase Cγ2 signalling pathway.Experimental and therapeutic medicine · 2020Article
- Role of HDACs in normal and malignant hematopoiesis.Molecular cancer · 2020Review
- Combined chemosensitivity and chromatin profiling prioritizes drug combinations in CLL.Nature chemical biology · 2019Article
- Silencing of HDAC6 as a therapeutic target in chronic lymphocytic leukemia.Blood advances · 2018Article
- Role and regulation of microRNAs targeting BTK in acute myelogenous leukemia.Leukemia & lymphoma · 2018Article
- Role of Bruton's tyrosine kinase in B cells and malignancies.Molecular cancer · 2018Review
- Mechanisms of Acquired Drug Resistance to the HDAC6 Selective Inhibitor Ricolinostat Reveals Rational Drug-Drug Combination with Ibrutinib.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Bruton's tyrosine kinase (BTK) is a critical mediator of survival in B-cell neoplasms. Although BTK inhibitors have transformed therapy in chronic lymphocytic leukemia (CLL), patients with high-risk genetics are at risk for relapse and have a poor prognosis. Identification of novel therapeutic strategies for this group of patients is an urgent unmet clinical need, and therapies that target BTK via alternative mechanisms may fill this niche. Herein, we identify a set of microRNAs (miRs) that target BTK in primary CLL cells and show that the histone deacetylase (HDAC) repressor complex is recruited to these miR promoters to silence their expression. Targeting the HDACs by using either RNA interference against HDAC1 in CLL or a small molecule inhibitor (HDACi) in CLL and mantle cell lymphoma restored the expression of the BTK-targeting miRs with loss of BTK protein and downstream signaling and consequent cell death. We have also made the novel and clinically relevant discovery that inhibition of HDAC induces the BTK-targeting miRs in ibrutinib-sensitive and resistant CLL to effectively reduce both wild-type and C481S-mutant BTK. This finding identifies a novel strategy that may be promising as a therapeutic modality to eliminate the C481S-mutant BTK clone that drives resistance to ibrutinib and provides the rationale for a combination strategy that includes ibrutinib to dually target BTK to suppress its prosurvival signaling.
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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.