ArticleBlood advances2022
Single-cell sequencing demonstrates complex resistance landscape in CLL and MCL treated with BTK and BCL2 inhibitors.
Article in Blood advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- [Advances in single cell omics applications in mantle cell lymphoma].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Review
- Resistance to targeted therapies in chronic lymphocytic leukemia: Current status and perspectives for clinical and diagnostic practice.Leukemia · 2025Review
- Single-cell Rapid Capture Hybridization sequencing reliably detects isoform usage and coding mutations in targeted genes.Genome research · 2025Article
- "The End of the Golden Weather": therapeutic strategies for mantle cell lymphoma relapsed or refractory to covalent BTK inhibitors.Haematologica · 2025Review
- Insights into genetic aberrations and signalling pathway interactions in chronic lymphocytic leukemia: from pathogenesis to treatment strategies.Biomarker research · 2024Review
- Passengers, drivers, and "goners".International journal of cancer · 2024Article
- Decoding leukemia at the single-cell level: clonal architecture, classification, microenvironment, and drug resistance.Experimental hematology & oncology · 2024Review
- Application and research progress of single cell sequencing technology in leukemia.Frontiers in oncology · 2024Review
- Pirtobrutinib in Covalent Bruton Tyrosine Kinase Inhibitor Pretreated Mantle-Cell Lymphoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Article
- Molecular associations of response to the new-generation BTK inhibitor zanubrutinib in marginal zone lymphoma.Blood advances · 2023Article
- Unresolved questions in selection of therapies for treatment-naïve chronic lymphocytic leukemia.Journal of hematology & oncology · 2023Review
- Landscape ofInternational journal of molecular sciences · 2023Article
- The end of the beginning: application of single-cell sequencing to chronic lymphocytic leukemia.Blood · 2023Review
- Article
- Article
- Enrichment of BTK Leu528Trp mutations in patients with CLL on zanubrutinib: potential for pirtobrutinib cross-resistance.Blood advances · 2022Article
- Tipping the balance: toward rational combination therapies to overcome venetoclax resistance in mantle cell lymphoma.Leukemia · 2022Review
- Successful Retreatment With Venetoclax in a Patient With Chronic Lymphocytic Leukemia.HemaSphere · 2022Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The genomic landscape of resistance to targeted agents (TAs) used as monotherapy in chronic lymphocytic leukemia (CLL) is complex and often heterogeneous at the patient level. To gain insight into the clonal architecture of acquired genomic resistance to Bruton tyrosine kinase (BTK) inhibitors and B-cell lymphoma 2 (BCL2) inhibitors in CLL, particularly in patients carrying multiple resistance mutations, we performed targeted single-cell DNA sequencing of 8 patients who developed progressive disease (PD) on TAs (either class). In all cases, analysis of single-cell architecture revealed mutual exclusivity between multiple resistance mutations to the same TA class, variable clonal co-occurrence of multiple mutations affecting different TAs in patients exposed to both classes, and a phenomenon of multiple independent emergences of identical nucleotide changes leading to canonical resistance mutations. We also report the first observation of established BCL2 resistance mutations in a patient with mantle cell lymphoma (MCL) following PD on sequential monotherapy, implicating BCL2 as a venetoclax resistance mechanism in MCL. Taken together, these data reveal the significant clonal complexity of CLL and MCL progression on TAs at the nucleotide level and confirm the presence of multiple, clonally independent, mechanisms of TA resistance within each individual disease context.
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