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Cited by 412Chronic Lymphocytic Leukemia ResearchLymphoma Diagnosis and TreatmentChronic Myeloid Leukemia Treatments

The B-cell receptor signaling pathway as a therapeutic target in CLL

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Woyach, Jennifer A., Johnson, Amy J., Byrd, John C.·2012·Blood
DOI 10.1182/blood-2012-02-362624PMC PMC3418714
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Abstract

Targeted therapy with imatinib and other selective tyrosine kinase inhibitors has transformed the treatment of chronic myeloid leukemia. Unlike chronic myeloid leukemia, chronic lymphocytic leukemia (CLL) lacks a common genetic aberration amenable to therapeutic targeting. However, our understanding of normal B-cell versus CLL biology points to differences in properties of B-cell receptor (BCR) signaling that may be amenable to selective therapeutic targeting. The applica-tion of mouse models has further expanded this understanding and provides information about targets in the BCR signaling pathway that may have other important functions in cell development or long-term health. In addition, overexpression or knockout of selected targets offers the potential to validate targets genetically using new mouse models of CLL. The initial success of BCR-targeted therapies has promoted much excitement in the field of CLL. At the present time, GS-1101, which reversibly inhibits PI3Kδ, and ibrutinib (PCI-32765), an irreversible inhibitor of Bruton tyrosine kinase, have generated the most promising early results in clinical trials including predominately refractory CLL where durable disease control has been observed. This review provides a summary of BCR signaling, tools for studying this pathway relevant to drug development in CLL, and early progress made with therapeutics targeting BCR-related kinases.

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  • TBX3 has previously been shown to directly interact with these signaling cascades in other cell types to regulate cell survival and proliferation.

    “TBX3 has previously been shown to directly interact with these signaling cascades in other cell types to regulate cell survival and proliferation [54–57]”

    From The oncoprotein TBX3 is controlling severity in experimental arthritis (2019) · cites this paper as [55]

    The section ‘Downstream activation pathways influenced by BCR’ (page unavailable) links MAPK and Akt signaling to cell survival and proliferation. It does not say that TBX3 directly interacts with those pathways in other cell types, which is the central interaction claimed here. (LLM, conf=0.84)

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Authors
Woyach, J. A., Johnson, A. J., & Byrd, J. C.
Affiliations
The Ohio State University (US)
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2012-08-09
Volume
120
Issue
6
Pages
1175-1184
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2012-02-362624
PMC
PMC3418714
OpenAlex
W1983395516
Cited by
412
References
4
Citations by year
2026: 7 · 2025: 16 · 2024: 21 · 2023: 23 · 2022: 16 · 2021: 30 · 2020: 26 · 2019: 24 · 2018: 33 · 2017: 32 · 2016: 27 · 2015: 31 · 2014: 53 · 2013: 60 · 2012: 13
FWCI
6.62
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • D. Warren Brown Family Foundation
  • National Institutes of Health (4p01ca081534-16)
  • National Cancer Institute (CA81534, P01CA095426, P50CA140158, P01 CA81534, CA95426, P01CA95426, CA140158, K12CA133250, P01-CA-081534)
Topics
  • Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
  • Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
Keywords
chronic lymphocytic leukemia, B cell receptor signaling, BTK inhibitors, ibrutinib, PI3Kδ inhibitor, tyrosine kinase inhibitors, drug discovery targets
MeSH terms
Animals, Cell Adhesion, Humans, Models, Biological, Receptors, Antigen, B-Cell, Signal Transduction, Leukemia, Lymphocytic, Chronic, B-Cell, Integrins, Mice, Validation Studies as Topic

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