ArticleBlood cancer discovery2021
Overcoming Acquired Epigenetic Resistance to BTK Inhibitors.
Article in Blood cancer discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 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
46 citing papers in PubMed, 57 citations in OpenAlex.
- Trial
- Acquired mutations in patients with relapsed/refractory CLL who progressed in the ALPINE study.Blood advances · 2025Trial
- Fat Mass and Obesity-Associated Protein Contributes to Tumorigenesis and Drug Resistance of Diffuse Large B-Cell Lymphoma by Suppressing N6-Methyladenosine Methylation of Myc.The Kaohsiung journal of medical sciences · 2026Article
- Acalabrutinib Versus Venetoclax Plus Obinutuzumab in Treatment-Naive Chronic Lymphocytic Leukemia: A Real-World Propensity Score-Matched Study.Cancer medicine · 2026Article
- The B-cell Receptor Blueprint in Lymphoma: Mechanisms and Therapeutic Opportunities.Blood cancer discovery · 2026Review
- Article
- Targeting signaling pathways in lymphoma: From molecular mechanisms to clinical breakthroughs.Chinese medical journal · 2026Review
- Exploiting tumor lineage features for precision cancer therapy.Trends in cancer · 2026Review
- Molecular Pathogenesis and Therapeutic Response of Diffuse Large B Cell Lymphoma Genetic Subtypes.Annual review of cancer biology · 2026Article
- Integrin-linked kinase (ILK) in hematologic malignancies: Bridging molecular mechanisms to therapeutic innovation.BioImpacts : BI · 2026Review
- Prolonged exposure to axitinib alters the molecular profile of Caki-2 renal cell carcinoma cells.Molecular and clinical oncology · 2025Article
- Expression of HERV-K and embryonic genes in chronic lymphocytic leukemia and their association with therapy regimens.Blood advances · 2025Article
- DyNDG: Identifying Leukemia-related Genes Based on Time-series Dynamic Network by Integrating Differential Genes.Genomics, proteomics & bioinformatics · 2025Article
- The Role of RAC2 and PTTG1 in Cancer Biology.Cells · 2025Review
- Single-cell RNA sequencing defines distinct disease subtypes and reveals hypo-responsiveness to interferon in asymptomatic Waldenstrom's Macroglobulinemia.Nature communications · 2025Article
- T Cells Spatially Regulate B Cell Receptor Signaling in Lymphomas through H3K9me3 Modifications.Advanced healthcare materials · 2025Article
- Longitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL.Nature communications · 2025Article
- Bruton's Tyrosine Kinase (BTK) Mutations in Chronic Lymphocytic Leukemia (CLL): A Clinical View.Mediterranean journal of hematology and infectious diseases · 2025Review
- Review
- Article
Corrections and comments
- Commented on by
Authors and funding
31 authors at 6 institutions in 2 countries.
Funding
Abstract
The use of Bruton tyrosine kinase (BTK) inhibitors to block B-cell receptor (BCR)-dependent NF-κB activation in lymphoid malignancies has been a major clinical advance, yet acquired therapeutic resistance is a recurring problem. We modeled the development of resistance to the BTK inhibitor ibrutinib in the activated B-cell (ABC) subtype of diffuse large B-cell lymphoma, which relies on chronic active BCR signaling for survival. The primary mode of resistance was epigenetic, driven in part by the transcription factor TCF4. The resultant phenotypic shift altered BCR signaling such that the GTPase RAC2 substituted for BTK in the activation of phospholipase Cγ2, thereby sustaining NF-κB activity. The interaction of RAC2 with phospholipase Cγ2 was also increased in chronic lymphocytic leukemia cells from patients with persistent or progressive disease on BTK inhibitor treatment. We identified clinically available drugs that can treat epigenetic ibrutinib resistance, suggesting combination therapeutic strategies. SIGNIFICANCE: In diffuse large B-cell lymphoma, we show that primary resistance to BTK inhibitors is due to epigenetic rather than genetic changes that circumvent the BTK blockade. We also observed this resistance mechanism in chronic lymphocytic leukemia, suggesting that epigenetic alterations may contribute more to BTK inhibitor resistance than currently thought.
Indexed as
Identifiers
What Socratic 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 Socratic graph.