ReviewExpert review of hematology2018
Are BTK and PLCG2 mutations necessary and sufficient for ibrutinib resistance in chronic lymphocytic leukemia?
Review in Expert review of hematology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 2 of them syntheses that pooled it.
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
44 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Efficacy and Effectiveness Outcomes of Treatments for Double-Exposed Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma Patients: A Systematic Literature Review.Cancer medicine · 2024Pooled it
- Resistance-Associated Mutations in Chronic Lymphocytic Leukemia Patients Treated With Novel Agents.Frontiers in oncology · 2020Pooled it
- Acquired mutations in patients with relapsed/refractory CLL who progressed in the ALPINE study.Blood advances · 2025Trial
- Trial
- Bendamustine, followed by ofatumumab and ibrutinib in chronic lymphocytic leukemia (CLL2-BIO): primary endpoint analysis of a multicenter, open-label phase-II trial.Haematologica · 2021Trial
- Bruton's Tyrosine Kinase Inhibitors: Mechanisms, Efficacy, Toxicities and Applications for the Treatment of Human Diseases.MedComm · 2026Review
- Mechanisms of resistance to BTK inhibitors in B cell malignancies and emerging targeted strategies.Molecular therapy. Oncology · 2026Review
- PLCG2 across human disease: genetic variants, signaling mechanisms, and clinical implications.Journal of translational medicine · 2026Review
- Resistance mechanisms and approach to chronic lymphocytic leukemia after BTK inhibitor therapy.Leukemia & lymphoma · 2025Review
- Aberrantly Expressed Mitochondrial Lipid Kinase, AGK, Activates JAK2-Histone H3 Axis and BCR Signal: A Mechanistic Study with Implication in CLL Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Longitudinal omics data and preclinical treatment suggest the proteasome inhibitor carfilzomib as therapy for ibrutinib-resistant CLL.Nature communications · 2025Article
- JNK1 inhibitors target distal B cell receptor signaling and overcome BTK-inhibitor resistance in CLL.The Journal of experimental medicine · 2025Article
- Bruton's Tyrosine Kinase Inhibitors: A Versatile Therapeutic Approach for Cancer, Autoimmune Disorders, GVHD and COVID-19.Mini reviews in medicinal chemistry · 2025Review
- Review
- A Review of Resistance Mechanisms to Bruton's Kinase Inhibitors in Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2024Review
- Treatment of Double-Refractory Chronic Lymphocytic Leukemia-An Unmet Clinical Need.International journal of molecular sciences · 2024Review
- Mutations Detected in Real World Clinical Sequencing during BTK Inhibitor Treatment in CLL.Research square · 2024Article
- BTK and PLCG2 remain unmutated in one-third of patients with CLL relapsing on ibrutinib.Blood advances · 2023Observational
- Duvelisib Eliminates CLL B Cells, Impairs CLL-Supporting Cells, and Overcomes Ibrutinib Resistance in a Xenograft Model.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Pirtobrutinib targets BTK C481S in ibrutinib-resistant CLL but second-site BTK mutations lead to resistance.Blood advances · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
introductionIbrutinib is the first BTK inhibitor to show efficacy in chronic lymphocytic leukemia (CLL) and is also the first BTK inhibitor to which patients have developed resistance. Mutations in BTK and PLCG2 are found in ≈80% of CLL patients with acquired resistance to ibrutinib, but it remains unclear if these mutations are merely associated with disease relapse or directly cause it. Areas covered: Unique properties of both CLL and ibrutinib that complicate attempts to definitively conclude whether BTK/PLCG2 mutations are passengers or drivers of ibrutinib-resistant disease are reviewed. Characteristics of mutations that drive drug resistance are summarized and whether BTK/PLCG2 mutations possess these is discussed. These characteristics include (1) identification in multiple patients with acquired resistance, (2) in vitro validation of drug-resistant properties, (3) mutual exclusivity with one another, (4) increasing frequency over time on drug, and (5) high frequency at the time and site of clinical relapse. Expert commentary: While BTK/PLCG2 mutations have characteristics suggesting that they can drive ibrutinib resistance, this conclusion remains formally unproven until specific inhibition of such mutations is shown to cause regression of ibrutinib-resistant CLL. Data suggest that alternative mechanisms of resistance do exist in some patients.
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.