scholarly journals Targeting the B-cell receptor signaling pathway in B lymphoid malignancies

2014 ◽  
Vol 21 (4) ◽  
pp. 341-349 ◽  
Author(s):  
Maike Buchner ◽  
Markus Müschen
Keyword(s):  
B Cell ◽  
Signaling Pathway ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Receptor Signaling ◽  
Lymphoid Malignancies ◽  
Receptor Signaling Pathway ◽  
B Cell Receptor Signaling ◽  
B Lymphoid ◽  
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 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

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 Pathogenic B‐cell receptor signaling in lymphoid malignancies: New insights to improve treatment

2019 ◽  
Vol 291 (1) ◽  
pp. 190-213 ◽  
Author(s):  
Ryan M. Young ◽  
James D. Phelan ◽  
Wyndham H. Wilson ◽  
Louis M. Staudt
Keyword(s):  
B Cell ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Receptor Signaling ◽  
Lymphoid Malignancies ◽  
Improve Treatment ◽  
B Cell Receptor Signaling ◽  
Cell Receptor Signaling
Sign in / Sign up

Export Citation Format

Share Document