Cytotoxic activity of the casein kinase 2 inhibitor CX-4945 against T-cell acute lymphoblastic leukemia: targeting the unfolded protein response signaling

Leukemia ◽  
2013 ◽  
Vol 28 (3) ◽  
pp. 543-553 ◽  
Author(s):  
F Buontempo ◽  
E Orsini ◽  
L R Martins ◽  
I Antunes ◽  
A Lonetti ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cytotoxic Activity ◽  
Unfolded Protein Response ◽  
Lymphoblastic Leukemia ◽  
Casein Kinase ◽  
Unfolded Protein ◽  
Cell Acute Lymphoblastic Leukemia ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Notch3 contributes to T-cell leukemia growth via regulation of the unfolded protein response

Oncogenesis ◽  
2020 ◽  
Vol 9 (10) ◽  
Author(s):  
Maria Valeria Giuli ◽  
Giulia Diluvio ◽  
Eugenia Giuliani ◽  
Giulia Franciosa ◽  
Laura Di Magno ◽  
...  
Keyword(s):  
T Cell ◽  
Er Stress ◽  
Unfolded Protein Response ◽  
Lymphoblastic Leukemia ◽  
Acute Leukemias ◽  
Unfolded Protein ◽  
Cell Acute Lymphoblastic Leukemia ◽  
The Unfolded Protein Response ◽  
Protein Response

Abstract Unfolded protein response (UPR) is a conserved adaptive response that tries to restore protein homeostasis after endoplasmic reticulum (ER) stress. Recent studies highlighted the role of UPR in acute leukemias and UPR targeting has been suggested as a therapeutic approach. Aberrant Notch signaling is a common feature of T-cell acute lymphoblastic leukemia (T-ALL), as downregulation of Notch activity negatively affects T-ALL cell survival, leading to the employment of Notch inhibitors in T-ALL therapy. Here we demonstrate that Notch3 is able to sustain UPR in T-ALL cells, as Notch3 silencing favored a Bip-dependent IRE1α inactivation under ER stress conditions, leading to increased apoptosis via upregulation of the ER stress cell death mediator CHOP. By using Juglone, a naturally occurring naphthoquinone acting as an anticancer agent, to decrease Notch3 expression and induce ER stress, we observed an increased ER stress-associated apoptosis. Altogether our results suggest that Notch3 inhibition may prevent leukemia cells from engaging a functional UPR needed to compensate the Juglone-mediated ER proteotoxic stress. Notably, in vivo administration of Juglone to human T-ALL xenotransplant models significantly reduced tumor growth, finally fostering the exploitation of Juglone-dependent Notch3 inhibition to perturb the ER stress/UPR signaling in Notch3-dependent T-ALL subsets.

scholarly journals Stressed: The Unfolded Protein Response in T Cell Development, Activation, and Function

2019 ◽  
Vol 20 (7) ◽  
pp. 1792 ◽  
Author(s):  
Kyeorda Kemp ◽  
Cody Poe
Keyword(s):  
Endoplasmic Reticulum ◽  
T Cell ◽  
Unfolded Protein Response ◽  
T Cell Development ◽  
Cell Development ◽  
Secretory Cells ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
And Function ◽  
Protein Response

The unfolded protein response (UPR) is a highly conserved pathway that allows cells to respond to stress in the endoplasmic reticulum caused by an accumulation of misfolded and unfolded protein. This is of great importance to secretory cells because, in order for proteins to traffic from the endoplasmic reticulum (ER), they need to be folded appropriately. While a wealth of literature has implicated UPR in immune responses, less attention has been given to the role of UPR in T cell development and function. This review discusses the importance of UPR in T cell development, homeostasis, activation, and effector functions. We also speculate about how UPR may be manipulated in T cells to ameliorate pathologies.

scholarly journals Cytotoxic activity of the novel Akt inhibitor, MK-2206, in T-cell acute lymphoblastic leukemia

Leukemia ◽  
2012 ◽  
Vol 26 (11) ◽  
pp. 2336-2342 ◽  
Author(s):  
C Simioni ◽  
L M Neri ◽  
G Tabellini ◽  
F Ricci ◽  
D Bressanin ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cytotoxic Activity ◽  
Lymphoblastic Leukemia ◽  
The Novel ◽  
Akt Inhibitor ◽  
Cell Acute Lymphoblastic Leukemia
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