|
Chronic Lymphocytic Leukemia
|
0.400 |
Biomarker
|
disease |
BEFREE |
Finally, we outline the key biologic and clinical responses to kinase inhibitor therapy, targeting the BCR-associated Bruton's tyrosine kinase, phosphoinositide-3-kinase, and spleen tyrosine kinase in patients with CLL.
|
30555163 |
2019 |
|
Chronic Lymphocytic Leukemia
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
Fostamatinib (R406) and entospletinib (GS-9973) are ATP-competitive inhibitors designed to target spleen tyrosine kinase (Syk) that have shown clinical activity with acceptable toxicity in trials with CLL patients.
|
28011996 |
2017 |
|
Chronic Lymphocytic Leukemia
|
0.400 |
Biomarker
|
disease |
BEFREE |
The observation that SYK inhibition also suppresses IL-10 provides a potential new rationale for therapeutic targeting and immunological rescue by SYK inhibitors in CLL.
|
27890932 |
2017 |
|
Chronic Lymphocytic Leukemia
|
0.400 |
Biomarker
|
disease |
BEFREE |
Current targeted agents in CLL are directed against B cell receptor-associated tyrosine kinases such as BTK and SYK, the downstream PI3-kinase pathway, as well as the antiapoptotic protein BCL-2.
|
28155013 |
2017 |
|
Chronic Lymphocytic Leukemia
|
0.400 |
Biomarker
|
disease |
BEFREE |
Syk protein, a tyrosine kinase essential for BCR signaling, is therefore a rational candidate for targeted therapy in CLL.
|
27888629 |
2017 |
|
Chronic Lymphocytic Leukemia
|
0.400 |
Biomarker
|
disease |
BEFREE |
Thus, SYK inhibition is a promising therapeutic strategy uniquely poised to antagonize crosstalk between BAFF and B-cell receptor, thereby disrupting the pro-survival microenvironment signaling in chronic lymphocytic leukemia.
|
28838991 |
2017 |
|
Chronic Lymphocytic Leukemia
|
0.400 |
Biomarker
|
disease |
BEFREE |
BCR signaling pathway inhibitors such as ibrutinib, idelalisib, and fostamatinib (respective inhibitors of Bruton's tyrosine kinase, PI3Kδ, and spleen tyrosine kinase) represent a significant therapeutic advance in B cell malignancies, including chronic lymphocytic leukemia (CLL).
|
25632006 |
2015 |
|
Chronic Lymphocytic Leukemia
|
0.400 |
Biomarker
|
disease |
BEFREE |
PLSR identified the relationship between upstream tyrosine kinase SYK and its target, PLCγ2, as maximally predictive and sufficient to distinguish CLL from healthy samples, pointing to this juncture in the signaling pathway as a hallmark of CLL B cells.
|
24489640 |
2014 |
|
Chronic Lymphocytic Leukemia
|
0.400 |
Biomarker
|
disease |
BEFREE |
Therefore, we here review the role of Syk in the pathogenesis of CLL and provide an update of progress in the clinical development of Syk inhibitors.
|
24547708 |
2014 |
|
Chronic Lymphocytic Leukemia
|
0.400 |
Biomarker
|
disease |
BEFREE |
BRAF inhibitor-driven ERK activity and CLL proliferation required B cell antigen receptor (BCR) activation, as inhibition of the BCR-proximal spleen tyrosine kinase (SYK) reversed ERK hyperactivation and proliferation of CLL cells from multiple patients, while inhibition of the BCR-distal Bruton tyrosine kinase had no effect.
|
25329694 |
2014 |
|
Chronic Lymphocytic Leukemia
|
0.400 |
Biomarker
|
disease |
BEFREE |
SYK blockade in CLL is a promising therapeutic principle not only for its inhibition of the BCR signaling pathway, but also by inhibiting protective stroma signals in a manner entirely independent of BCR signaling.
|
20335218 |
2010 |
|
Chronic Lymphocytic Leukemia
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
Therefore, the downregulation of ZAP-70 and P-SYK per se during treatment with GCs is not sufficient to induce apoptosis, and different mechanisms must therefore be responsible for the increased steroid sensitivity of ZAP-70+ CLL.
|
19297020 |
2009 |
|
Chronic Lymphocytic Leukemia
|
0.400 |
AlteredExpression
|
disease |
BEFREE |
Immunoblotting showed increased expression and phosphorylation of SYK, PLCgamma(2), signal transducers and activators of transcription 3, and extracellular signal regulated kinase 1/2 in CLL compared with healthy B cells, suggesting enhanced activation of these mediators in CLL.
|
19549911 |
2009 |
|
Chronic Lymphocytic Leukemia
|
0.400 |
Biomarker
|
disease |
BEFREE |
We conclude that Syk constitutes a key regulator of B-CLL cell survival, emphasizing the clinical utility of Syk inhibition in hematopoietic malignancies.
|
19581935 |
2009 |
|
Chronic Lymphocytic Leukemia
|
0.400 |
GenomicAlterations
|
disease |
CGI |
|
|
|