ArticleNature communications2016
Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 201 papers, 2 of them syntheses that pooled it.
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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
201 citing papers in PubMed, 2 syntheses or guidelines pooled it, 341 citations in OpenAlex.
- Real‑life diagnostic and therapeutic approach to CLL/SLL in tuscany: the 2025 consensus.Clinical and experimental medicine · 2026Guideline
- Resistance-Associated Mutations in Chronic Lymphocytic Leukemia Patients Treated With Novel Agents.Frontiers in oncology · 2020Pooled it
- Prediction of Outcome in Patients With Chronic Lymphocytic Leukemia Treated With Ibrutinib: Development and Validation of a Four-Factor Prognostic Model.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Trial
- Venetoclax Plus Rituximab in Relapsed Chronic Lymphocytic Leukemia: 4-Year Results and Evaluation of Impact of Genomic Complexity and Gene Mutations From the MURANO Phase III Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Trial
- Genomic evolution of ibrutinib-resistant clones in Waldenström macroglobulinaemia.British journal of haematology · 2020Trial
- Genomic alterations in high-risk chronic lymphocytic leukemia frequently affect cell cycle key regulators and NOTCH1-regulated transcription.Haematologica · 2020Trial
- Ibrutinib therapy downregulates AID enzyme and proliferative fractions in chronic lymphocytic leukemia.Blood · 2019Trial
- Depth and durability of response to ibrutinib in CLL: 5-year follow-up of a phase 2 study.Blood · 2018Trial
- Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia.Nature communications · 2018Trial
- Venetoclax for chronic lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial.The Lancet. Oncology · 2018Trial
- The evolutionary landscape of chronic lymphocytic leukemia treated with ibrutinib targeted therapy.Nature communications · 2017Trial
- Acquired mutations associated with ibrutinib resistance in Waldenström macroglobulinemia.Blood · 2017Trial
- Trial
- Bruton's Tyrosine Kinase Inhibitors: Mechanisms, Efficacy, Toxicities and Applications for the Treatment of Human Diseases.MedComm · 2026Review
- Mutational and copy number analysis at diagnosis and relapse of mantle cell lymphoma.Haematologica · 2026Article
- Precision Medicine in Non-Hodgkin Lymphoma: Advances in BTK Inhibition, CD30-Directed Antibody-Drug Conjugates, and HDAC-Mediated Epigenetic Therapy with Pirtobrutinib, Brentuximab Vedotin, and Belinostat.Journal of clinical medicine · 2026Review
- Resistance pathways and next-generation treatments in chronic lymphocytic leukemia.Discover oncology · 2026Review
- Mutant ribosomal protein RPS15 drives B cell malignancy through oxidative stress and genomic instability.Nature communications · 2026Article
- UVI5008: the first reversible, non-covalent Bruton's tyrosine kinase epi-inhibitor for B-cell malignancies.Journal of hematology & oncology · 2026Article
- Co-mapping clonal and transcriptional heterogeneity in somatic evolution via GoT-Multi.Cell genomics · 2026Article
141 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
41 authors at 8 institutions in 3 countries.
Funding
Abstract
Resistance to the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has been attributed solely to mutations in BTK and related pathway molecules. Using whole-exome and deep-targeted sequencing, we dissect evolution of ibrutinib resistance in serial samples from five chronic lymphocytic leukaemia patients. In two patients, we detect BTK-C481S mutation or multiple PLCG2 mutations. The other three patients exhibit an expansion of clones harbouring del(8p) with additional driver mutations (EP300, MLL2 and EIF2A), with one patient developing trans-differentiation into CD19-negative histiocytic sarcoma. Using droplet-microfluidic technology and growth kinetic analyses, we demonstrate the presence of ibrutinib-resistant subclones and estimate subclone size before treatment initiation. Haploinsufficiency of TRAIL-R, a consequence of del(8p), results in TRAIL insensitivity, which may contribute to ibrutinib resistance. These findings demonstrate that the ibrutinib therapy favours selection and expansion of rare subclones already present before ibrutinib treatment, and provide insight into the heterogeneity of genetic changes associated with ibrutinib resistance.
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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.