scholarly journals ZFP521 contributes to pre-B-cell lymphomagenesis through modulation of the pre-B-cell receptor signaling pathway

Oncogene ◽  
2015 ◽  
Vol 35 (25) ◽  
pp. 3227-3238 ◽  
Author(s):  
T Hiratsuka ◽  
Y Takei ◽  
R Ohmori ◽  
Y Imai ◽  
M Ozeki ◽  
...  
Keyword(s):  
B Cell ◽  
Signaling Pathway ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Receptor Signaling ◽  
Receptor Signaling Pathway ◽  
B Cell Receptor Signaling ◽  
Cell Receptor Signaling

An HSP90 Inhibitor, PU-H71, Antagonizes Stroma-Induced Pro-Survival Effects in CLL through Its Inhibition of Multi-Component B-Cell Receptor Signaling Pathway

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5289-5289
Author(s):  
Ailin Guo ◽  
Pin Lu ◽  
Chaojie Zhen ◽  
Gabriela Chiosis ◽  
Yue Lynn Wang
Keyword(s):  
B Cell ◽  
Signaling Pathway ◽  
Cell Receptor ◽  
Hsp90 Inhibitor ◽  
B Cell Receptor ◽  
Receptor Signaling ◽  
Bcr Signaling ◽  
Receptor Signaling Pathway ◽  
B Cell Receptor Signaling ◽  
Cell Receptor Signaling

Abstract Background: Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of B-cells in the hematopoietic system. The B-cell receptor (BCR) plays an essential role in the pathogenesis of CLL and many components of the BCR signaling pathway are known clients of HSP90. HSP90 is a highly conserved molecular chaperone that ensures the proper folding and stabilization of its client proteins. In this study, we investigated whether PU-H71 a novel purine-scaffold HSP90 Inhibitor, has anti-tumor activity in CLL by destabilizing BCR signaling pathway constituents. Design: Fresh CLL cells were isolated and cultured ex vivo with or without stromal co-culture. Molecular and cellular events were studied in PU-H71-treated and control CLL cells. Results: Immunoblotting revealed that a significantly higher amount of HSP90 is present in CLL cells than in peripheral blood mononuclear cells (PBMC), suggesting the chaperone is pathogenically relevant. We found that PU-H71 caused the death of CLL cells in a dose and time dependent manner while the viability of either PBMC or normal B lymphocytes were not affected. PU-H71 induced apoptosis resulting in CLL cell death as it caused mitochondrial cytochrome C release and a decrease in the abundance of several anti-apoptotic proteins. Interestingly, PU-H71 has the ability to counteract the pro-survival effects of the stroma and caused apoptosis in CLL cells co-cultured with stroma. To gain mechanistic insights into how PU-H71 acts, we examined the BCR signaling pathway. We found that the amounts of several key components of the pathway were reduced by PU-H71 treatment. This occurred even in the presence of stromal co-culture. The results suggest that PU-H71 antagonizes the function of HSP90 leading to the destabilization of the BCR signaling transducers. A chemical pull-down experiment revealed the co-existence of the BCR components and HSP90 in the same complex, suggesting these BCR constituents are indeed clients of HSP90 in CLL cells. Further, specific genetic knock-down of the signal transducers by siRNA confirmed their key roles in mediating the survival of CLL cells. Conclusions: PU-H71 antagonizes stroma-induced pro-survival effects in CLL through its inhibition of the B-cell receptor signaling pathway. Our results suggest that PU-H71 may serve as a useful therapy against CLL and is worth further clinical development. Disclosures No relevant conflicts of interest to declare.

scholarly journals Racial differences in B cell receptor signaling pathway activation

2012 ◽  
Vol 10 (1) ◽  
Author(s):  
Diane M Longo ◽  
Brent Louie ◽  
Kavita Mathi ◽  
Zoltan Pos ◽  
Ena Wang ◽  
...  
Keyword(s):  
B Cell ◽  
Signaling Pathway ◽  
Racial Differences ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Receptor Signaling ◽  
Pathway Activation ◽  
Receptor Signaling Pathway ◽  
B Cell Receptor Signaling ◽  
Cell Receptor Signaling

PPP3CC gene: a putative modulator of antidepressant response through the B-cell receptor signaling pathway

2014 ◽  
Vol 14 (5) ◽  
pp. 463-472 ◽  
Author(s):  
C Fabbri ◽  
A Marsano ◽  
D Albani ◽  
A Chierchia ◽  
R Calati ◽  
...  
Keyword(s):  
B Cell ◽  
Signaling Pathway ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Receptor Signaling ◽  
Antidepressant Response ◽  
Receptor Signaling Pathway ◽  
B Cell Receptor Signaling ◽  
Cell Receptor Signaling

scholarly journals The BAFF Receptor Transduces Survival Signals by Co-opting the B Cell Receptor Signaling Pathway

Immunity ◽  
2013 ◽  
Vol 38 (3) ◽  
pp. 475-488 ◽  
Author(s):  
Edina Schweighoffer ◽  
Lesley Vanes ◽  
Josquin Nys ◽  
Doreen Cantrell ◽  
Scott McCleary ◽  
...  
Keyword(s):  
B Cell ◽  
Signaling Pathway ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Receptor Signaling ◽  
Receptor Signaling Pathway ◽  
B Cell Receptor Signaling ◽  
Cell Receptor Signaling ◽  
Survival Signals

scholarly journals Dramatic Response with Single-Agent Ibrutinib in Multiply Relapsed Marginal Zone Lymphoma with MYD88L265P Mutation

2017 ◽  
Vol 10 (3) ◽  
pp. 813-818 ◽  
Author(s):  
Ryan C. Lynch ◽  
Ranjana H. Advani
Keyword(s):  
B Cell ◽  
Signaling Pathway ◽  
Marginal Zone ◽  
Single Agent ◽  
Cell Receptor ◽  
Marginal Zone Lymphoma ◽  
B Cell Receptor ◽  
Receptor Signaling Pathway ◽  
B Cell Receptor Signaling ◽  
Cell Receptor Signaling

The B-cell receptor signaling pathway is important in the lymphomagenesis of many lymphomas, including marginal zone lymphoma (MZL). Herein we describe a case of extranodal MZL refractory to multiple lines of therapy. The presence of an IgM paraprotein prompted further evaluation, and the patient was found to have an MYD88L265P mutation. Treatment with ibrutinib led to a dramatic response with prompt resolution of symptoms and significant improvement in measurable sites of disease. The excellent response to ibrutinib in our patient with MYD88L265P-mutated refractory MZL supports a biological rationale for its use.

Sign in / Sign up

Export Citation Format

Share Document