AI Article Synopsis
- Chronic lymphocytic leukemia (CLL) B cells depend on interactions with non-malignant cells and the tissue environment for survival and growth, mediated by specific receptors like BCR and CXCR4.
- Activation of these receptors triggers Bruton's tyrosine kinase (BTK), which helps prevent cell death and promotes growth, allowing cells to receive supportive signals.
- Ibrutinib, a BTK inhibitor, effectively helps patients with CLL and some lymphomas by blocking these supportive signals rather than causing cell death.
Article Abstract
The leukemic B cells from patients with chronic lymphocytic leukemia (CLL) require interactions with non-malignant cells and matrix in the tissue microenvironment to survive and grow. These interactions are mediated through the B-cell antigen receptor (BCR), C-X-C chemokine receptor type 4 (CXCR4), and a variety of integrins, including VLA-4. Exciting each receptor type leads to activation of Bruton's tyrosine kinase (BTK), which in turn helps initiate trophic signals that prevent cell death and promote cell activation and growth as well as allowing cells to return to anatomic sites for rescue signals. These represent the two major functional actions targeted by inhibitors of Btk. Here we relate some of the therapeutic actions of ibrutinib, a Btk inhibitor that is extremely helpful for patients with CLL, certain Diffuse Large B-cell Lymphomas (ABC type), and other non-Hodgkin's lymphomas, emphasizing that ibrutinib's value results from blocking beneficial signals, not by inducing lethal ones.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/hon.3144 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
BTK inhibition in primary central nervous system lymphoma: mechanisms, clinical efficacy, and future perspectives.
Front Oncol
December 2024
Thoracic Oncology Ward, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
The prognosis of primary central nervous system lymphoma (PCNSL) patients is relatively poor, and there is currently no standard treatment plan. Most patients choose high-dose chemotherapy based on methotrexate. While traditional chemotherapy combined with biological therapy has achieved limited results, some patients still do not respond to treatment or cannot tolerate its toxicity and side effects.
View Article and Find Full Text PDFA Novel Triplet of Alisertib Plus Ibrutinib Plus Rituximab Is Active in Mantle Cell Lymphoma.
Cancers (Basel)
December 2024
Division of Hematology/Oncology, Department of Medicine, Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
: Aurora (AK) A/B are oncogenic mitotic kinases that when over-expressed are poor prognostic markers in mantle cell lymphoma (MCL). : Alisertib, an AK-A inhibitor, has anti-tumor activity in relapsed/refractory (r/r) MCL patients. We evaluated alisertib plus ibrutinib in MCL to abrogate ibrutinib resistance.
View Article and Find Full Text PDFInhibition of proteolytic and ATPase activities of the proteasome by the BTK inhibitor CGI-1746.
iScience
November 2024
Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, 720 S. Donahue Dr., Auburn, AL, USA.
Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, has been shown to synergize with proteasome inhibitors (PIs) in reducing the viability of cells derived from B cell malignancies, but the mechanism is not known. We report here that an off-target effect of ibrutinib causes synergy because not all BTK inhibitors exhibited the synergistic effect, and those that synergized did so even in cells that do not express BTK. The allosteric BTK inhibitor CGI-1746 showed the strongest synergy.
View Article and Find Full Text PDFPharmacological Management of IgG4-Related Disease: From Traditional to Mechanism-Based Targeted Therapies.
Drugs Aging
January 2025
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
IgG4-related disease (IgG4-RD) is an immune-mediated disorder characterized by organ enlargement and dysfunction. The formation of tertiary lymphoid tissues (TLTs) in affected organs is crucial for understanding IgG4-RD, as T follicular helper (Tfh) 2 cells within TLTs drive IgG4+B cell differentiation, contributing to mass formation. Key cytokines IL-4 and IL-10, produced by Tfh2 cells, are essential for this process.
View Article and Find Full Text PDFInhibition of Bruton's tyrosine kinase restricts neuroinflammation following intracerebral hemorrhage.
Theranostics
January 2025
Department of Neurology, Tianjin Neurological Institute, Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, International Joint Laboratory of Ocular Diseases, Ministry of Education, Haihe Laboratory of Cell Ecosystem, Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous System Tianjin & Ministry of Education, Tianjin Medical University General Hospital, Tianjin 300052, China.
Intracerebral hemorrhage (ICH) is a devastating form of stroke with a lack of effective treatments. Following disease onset, ICH activates microglia and recruits peripheral leukocytes into the perihematomal region to amplify neural injury. Bruton's tyrosine kinase (BTK) controls the proliferation and survival of various myeloid cells and lymphocytes.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!