ArticleOncogene2009
The tyrosine kinase Syk regulates the survival of chronic lymphocytic leukemia B cells through PKCdelta and proteasome-dependent regulation of Mcl-1 expression.
Article in Oncogene, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 114 citations in OpenAlex.
- Visomitin as a differentiation-inducing therapeutic agent through SYK inhibition in AML.Frontiers in pharmacology · 2026Article
- Drug-Induced Differential Gene Expression Analysis on Nanoliter Droplet Microarrays: Enabling Tool for Functional Precision Oncology.Advanced healthcare materials · 2025Article
- An Update on Protein Kinases as Therapeutic Targets-Part I: Protein Kinase C Activation and Its Role in Cancer and Cardiovascular Diseases.International journal of molecular sciences · 2023Review
- The Neuropilin-1/PKC axis promotes neuroendocrine differentiation and drug resistance of prostate cancer.British journal of cancer · 2023Article
- Loss of NF1 in Melanoma Confers Sensitivity to SYK Kinase Inhibition.Cancer research · 2023Article
- High surface IgM levels associate with shorter response to ibrutinib and BTK bypass in patients with CLL.Blood advances · 2022Article
- GSK3β is a critical, druggable component of the network regulating the active NOTCH1 protein and cell viability in CLL.Cell death & disease · 2022Article
- Article
- CD160 receptor in CLL: Current state and future avenues.Frontiers in immunology · 2022Review
- Review
- Constitutive activation of Lyn kinase enhances BCR responsiveness, but not the development of CLL in Eµ-TCL1 mice.Blood advances · 2020Article
- Cell Death Pathways in Lymphoid Malignancies.Current oncology reports · 2020Review
- IL-17A Increases Multiple Myeloma Cell Viability by Positively Regulating Syk Expression.Translational oncology · 2019Article
- Review
- SYK Inhibition Potentiates the Effect of Chemotherapeutic Drugs on Neuroblastoma Cells in Vitro.Cancers · 2019Article
- CXCR4- and BCR-triggered integrin activation in B-cell chronic lymphocytic leukemia cells depends on JAK2-activated Bruton's tyrosine kinase.Oncotarget · 2018Article
- IL-4 enhances survival of in vitro-differentiated mouse basophils through transcription-independent signaling downstream of PI3K.Cell death & disease · 2018Article
- Comparison of the mRNA expression profile of B-cell receptor components in normal CD5-high B-lymphocytes and chronic lymphocytic leukemia: a key role of ZAP70.Cancer medicine · 2017Article
- Macrophages confer survival signals via CCR1-dependent translational MCL-1 induction in chronic lymphocytic leukemia.Oncogene · 2017Article
- Over expression of proteins that alter the intracellular signaling pathways in the cytoplasm of the liver cells forming Mallory-Denk bodies.Experimental and molecular pathology · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
B-cell chronic lymphocytic leukemia (B-CLL) is characterized by accumulation of mature monoclonal CD5+ B cells. The disease results mainly from a failure of cells to undergo apoptosis, a process largely influenced by the existence of constitutively activated components of B-cell receptor signaling and the deregulated expression of anti-apoptotic molecules. Recent evidence pointing to a critical role of spleen tyrosine kinase (Syk) in ligand-independent BCR signaling prompted us to examine its role in primary B-CLL cell survival. We demonstrate that pharmacological inhibition of constitutive Syk activity and silencing by siRNA led to a dramatic decrease of cell viability in CLL samples (n=44), regardless of clinical and biological status and induced typical apoptotic cell death with mitochondrial failure followed by caspase 3-dependent cell death. We also provide functional and biochemical evidence that Syk regulated B-CLL cell survival through a novel pathway involving PKCdelta and a proteasome-dependent regulation of the anti-apoptotic protein Mcl-1. Together, our observations are consistent with a model wherein PKCdelta downstream of Syk stabilizes Mcl-1 through inhibitory phosphorylation of GSK3 by Akt. We conclude that Syk constitutes a key regulator of B-CLL cell survival, emphasizing the clinical utility of Syk inhibition in hematopoietic malignancies.
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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.