BTKCys481Ser drives ibrutinib resistance via ERK1/2 and protects BTKwild-type MYD88-mutated cells by a paracrine mechanism
Abstract
Key Points: BTKCys481 mutation results in ERK1/2 mediated survival signaling and ibrutinib resistance in MYD88-mutated cells. BTKCys481 mutation confers a protective effect against ibrutinib on neighboring BTK wild-type cells through a paracrine mechanism.
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WM cells with BTK C481S confer protection against ibrutinib to neighboring BTK WT cells in vitro via a paracrine mechanism involving activation of extracellular signal-regulated kinase (ERK) 1/2.
“It was demonstrated that WM cells with BTK C481S confer protection against ibrutinib to neighboring BTK WT cells in vitro via a paracrine mechanism involving activation of extracellular signal–regulated kinase (ERK) 1/2(44).”
From Resistance Mechanisms and Approach to Chronic Lymphocytic Leukemia after BTK Inhibitor Therapy (2025) · cites this paper as [44]
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References 41 · Cited by 88
- Authors
- Chen, J. G., Liu, X., Munshi, M., Xu, L., Tsakmaklis, N., Demos, M. G., Kofides, A., Guerrera, M. L., Chan, G. G., Patterson, C. J., Meid, K., Gustine, J., Dubeau, T., Severns, P., Castillo, J. J., Hunter, Z. R., Wang, J., Buhrlage, S. J., Gray, N. S., Treon, S. P., & Yang, G.
- Affiliations
- Bing Center for Waldenstrom’s Macroglobulinemia,
- Dana-Farber Cancer Institute (US)
- Harvard University (US)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2018-05-03
- Volume
- 131
- Issue
- 18
- Pages
- 2047-2059
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2792386849
- Cited by
- 88
- References
- 41
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 11 · 2023: 9 · 2022: 8 · 2021: 15 · 2020: 13 · 2019: 9 · 2018: 5
- FWCI
- 5.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Applied Materials
- Pharmacyclics
- Topics
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Keywords
- Bruton's tyrosine kinase, ibrutinib resistance, ERK signaling, MYD88 mutation, paracrine signaling, survival signaling, Waldenström macroglobulinemia, BTK inhibitors
- MeSH terms
- Agammaglobulinaemia Tyrosine Kinase, Adenine, Cell Survival, Humans, Mutation, Piperidines, Pyrazoles, Pyrimidines, Cytokines, Apoptosis, Inflammation Mediators, Drug Resistance, Neoplasm, Paracrine Communication, MAP Kinase Signaling System, Cell Line, Tumor, Myeloid Differentiation Factor 88
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