ArticleAmerican journal of blood research2013
Bruton's tyrosine kinase mediated signaling enhances leukemogenesis in a mouse model for chronic lymphocytic leukemia.
Article in American journal of blood research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 58 citations in OpenAlex.
- Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia: Results of the First Randomized Phase III Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Trial
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- Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL.The New England journal of medicine · 2018Trial
- Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia.The New England journal of medicine · 2016Trial
- Ibrutinib-induced lymphocytosis in patients with chronic lymphocytic leukemia: correlative analyses from a phase II study.Leukemia · 2014Trial
- Trial
- Strong constitutive NF-κB signaling in B cells drives SLL/CLL-like lymphomagenesis and overcomes microenvironmental dependencies.Leukemia · 2026Article
- Chronic lymphocytic leukemia: criteria for first-line therapeutic choice-an opinion paper.Medical oncology (Northwood, London, England) · 2025Review
- Autoimmunity promotes chronic lymphocytic leukemia progression in an indolent disease model.Scientific reports · 2025Article
- Targeted protein degradation in hematologic malignancies: clinical progression towards novel therapeutics.Biomarker research · 2024Review
- Treatment of Double-Refractory Chronic Lymphocytic Leukemia-An Unmet Clinical Need.International journal of molecular sciences · 2024Review
- Preclinical characterization of pirtobrutinib, a highly selective, noncovalent (reversible) BTK inhibitor.Blood · 2023Article
- Structural Complementarity of Bruton's Tyrosine Kinase and Its Inhibitors for Implication in B-Cell Malignancies and Autoimmune Diseases.Pharmaceuticals (Basel, Switzerland) · 2023Review
- BTK inhibitors in the treatment of hematological malignancies and inflammatory diseases: mechanisms and clinical studies.Journal of hematology & oncology · 2022Review
- Ibrutinib in the Treatment of Solid Tumors: Current State of Knowledge and Future Directions.Cells · 2022Review
- Bruton's tyrosine kinase inhibition induces rewiring of proximal and distal B-cell receptor signaling in mice.European journal of immunology · 2021Article
- The nonreceptor tyrosine kinase SRMS inhibits autophagy and promotes tumor growth by phosphorylating the scaffolding protein FKBP51.PLoS biology · 2021Article
- Review
- Review
- Ibrutinib in Chronic Lymphocytic Leukemia: Clinical Applications, Drug Resistance, and Prospects.OncoTargets and therapy · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In chronic lymphocytic leukemia (CLL) signals from the B cell receptor (BCR) play a major role in disease development and progression. In this light, new therapies that specifically target signaling molecules downstream of the BCR continue to be developed. While first studies on the selective small molecule inhibitor of Bruton's tyrosine kinase (Btk), Ibrutinib (PCI-32765), demonstrated that Btk inhibition sensitizes CLL cells to apoptosis and alters their migratory behavior, these studies however did not address whether Btk-mediated signaling is involved in the process of CLL leukemogenesis. To investigate the requirement of Btk signaling for CLL development, we modulated Btk expression in the IgH.ETμ CLL mouse model, which is based on sporadic expression of the simian oncovirus SV40 T-antigen in mature B cells. To this end, we crossed IgH.ETμ mice on a Btk-deficient background or introduced a human Btk transgene (CD19-hBtk). Here we show that Btk deficiency fully abrogates CLL formation in IgH.ETμ mice, and that leukemias formed in Btk haplo-insufficient mice selectively expressed the wild-type Btk allele on their active X chromosome. Conversely, Btk overexpression accelerated CLL onset, increased mortality, and was associated with selection of non-stereotypical BCRs into CLL clones. Taken together, these data show that Btk expression represents an absolute prerequisite for CLL development and that Btk mediated signaling enhances leukemogenesis in mice. We therefore conclude that in CLL Btk expression levels set the threshold for malignant transformation.
Indexed as
Identifiers
23359016PMC3555194W1601587199What 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.