Blood Adv. New roles for B cell receptor associated kinases: when the B cell is not the target. Such studies have provided clues suggesting new pathogenic mechanisms for the disordered immunoglobulin synthesis in patients with immunodeficiency, autoimmunity, and malignancy. This site needs JavaScript to work properly. The B‐cell receptor signaling pathway, which is critical to the development and maturation of normal B‐cells, is emerging as an attractive therapeutic target in B‐cell malignancies. Antigen engagement by the BCR results in the formation of a micro-signalosome whereby BTK activates four families of non-receptor protein tyrosine kinases that transduce key signaling events including phospholipase Cγ, mitogen-activated protein kinase (MAPK) activation, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-кB) pathway components and activation of the serine/threonine kinase AKT (PKB). Introduction: Over the last few years, several new synthetic drugs, particularly Bruton’s tyrosine kinase (BTK), phosphatidylinositol 3-kinase (PI3K) and BCL-2 inhibitors have been developed and investigated in chronic lymphocytic leukemia (CLL). Simar Pal Singh, Floris Dammeijer & Rudi W. Hendriks Research over the role of Bruton’s agammaglobulinemia tyrosine kinase (BTK) in B-lymphocyte development, differentiation, signaling and survival has led to better understanding of the pathogenesis of B-cell malignancies. (2012). that platelets of the majority of the patients (37 out of 45 families) had decreased or absent Btk expression, and that platelets from carrier females of these families had both normal and mutated Btk expression, indicating that megakaryocytes in XLA carriers undergo random X-chromosome inactivation. Epub 2019 Jan 30. M. Takata, T. KurosakiA role for Bruton’s tyrosine kinase in B cell antigen receptor-mediated activation of phospholipase C-γ2 J Exp Med, 184 (1996), pp. Interpretation: Role of Bruton’s tyrosine kinase downstream of the B cell receptor. (2)Department of Immunology, Rotterdam, The Netherlands. 2020 Dec 8;4(23):6009-6018. doi: 10.1182/bloodadvances.2020003010. Zanubrutinib for the treatment of MYD88 wild-type Waldenström macroglobulinemia: a substudy of the phase 3 ASPEN trial. Role of Bruton’s tyrosine kinase in B cells and malignancies The authors declare that they have no competing interests. Bruton's tyrosine kinase (BTK) is a key component of B cell receptor (BCR) signalling and functions as an important regulator of cell proliferation and cell survival in various B cell malignancies. Down-regulation of BTK activity is an attractive novel strategy for treating patients with B-cell malignancies. BTK was initially shown to be defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) and is essential both for B cell development and function of mature B cells. In older subjects with COPD, bacterial lysates seem to have a positive effect on lung health. Haematologica. Bruton’s tyrosine kinase inhibitors have demonstrated a well-tolerated safety and efficacy profile across several B-cell malignancies. BTK was initially shown to be defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) and is essential both for B cell development and function of mature B cells. A preview of this full-text is provided by Springer Nature. Department of Pulmonary Medicine, Room Ee2251a, Erasmus MC Rotterdam, PO Box 2040, NL 3000, CA, Rotterdam, The Netherlands. 2019 Apr 3;18(1):79. doi: 10.1186/s12943-019-1009-z. Year: 2018. These studies have also brought to light new pathogenic mechanisms that underlie certain forms of primary immunodeficiency disease, as well as autoimmune, malignant, and allergic disorders. 2020 Dec 11;10(12):344. doi: 10.3390/life10120344. 2015;125:1780–1789. Affiliations. Would you like email updates of new search results? Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis, Multiomics Integration Elucidates Metabolic Modulators of Drug Resistance in Lymphoma, Increased sensitivity of BCR-ABL-induced B-ALL to imatinib by releasing leukemia B cell differentiation blockage, Immune-Based Therapies and the Role of Microsatellite Instability in Pancreatic Cancer, Targeted Therapy for Infectious Disease − A Case for Phosphoinositide 3-Kinase, Cardiotoxicity of Novel Targeted Hematological Therapies, Emerging Kinase Therapeutic Targets in Pancreatic Ductal Adenocarcinoma and Pancreatic Cancer Desmoplasia, Severe platelet dysfunction in NHL patients receiving ibrutinib is absent in patients receiving acalabrutinib, Cumulative incidence, risk factors, and management of atrial fibrillation in patients receiving ibrutinib, Pathogen‐specific B‐cell receptors drive chronic lymphocytic leukemia by light‐chain‐dependent cross‐reaction with autoantigens, Ig V Gene Mutation Status and CD38 Expression As Novel Prognostic Indicators in Chronic Lymphocytic Leukemia, Five-Year Experience with Single-Agent Ibrutinib in Patients with Previously Untreated and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia, Targeting B cell receptor signalling in cancer: Preclinical and clinical advances, Systematic review of infectious events with the BTK inhibitor ibrutinib in the treatment of haematologic malignancies, Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): A single-arm, multicentre, phase 2 trial, Bruton’s tyrosine kinase inhibitors: First and second generation agents for patients with Chronic Lymphocytic Leukemia (CLL), Novel synthetic drugs currently in clinical development for chronic lymphocytic leukemia, Breathe study (BronchoVaxom in adolescents and adults with asthma), The aging immune system and nutritional interventions. 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