The Acetyltransferase KAT5 Inhibitor NU 9056 Promotes Apoptosis and Inhibits JAK2/STAT3 Pathway in Extranodal NK/T Cell Lymphoma

2021 ◽  
Vol 21 ◽  
Author(s):  
Linyan Xu ◽  
Yuanyuan Qin ◽  
Mengdi Liu ◽  
Jun Jiao ◽  
Dongyun Tu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Signalling Pathway ◽  
Natural Killer T Cell ◽  
M Phase ◽  
Induced Apoptosis ◽  
Stat3 Signalling ◽  
Killer T Cell

Background: Extranodal natural killer/T cell lymphoma (ENKTL) is an aggressive malignant non-Hodgkin's lymphoma (NHL) with a poor prognosis. Therefore, novel therapeutic biomarkers and agents must be identified for the same. KAT5 inhibitor, NU 9056, is a small molecule that can inhibit cellular proliferation; however, its role in ENKTL has not been studied. Objective: The present study investigated the effect of NU 9056 in ENKTL cells and explored the possible molecular mechanism for its antitumour effect. Methods: The role of NU 9056 in ENKTL cells was investigated through the Cell Counting Kit-8 assay, flow cytometry, Western blot, and real-time quantitative polymerase chain reaction assay. Results: NU 9056 inhibited ENKTL cell proliferation and induced G2/M phase arrest. NU 9056 also induced apoptosis by upregulating DR4, DR5, and caspase 8 expressions. Additionally, NU 9056 increased the expression of Bax, Bid, and cytochrome C and decreased the expression of Bcl-2, Mcl-1, and XIAP. Furthermore, NU 9056 activated endoplasmic reticulum (ER) stress and inhibited the JAK2/STAT3 signalling pathway. The p38 mitogen-activated protein kinase (MAPK) signalling pathway was also activated by NU 9056, and the ERK signalling pathway was suppressed in natural killer/T cell lymphoma cells. Conclusion: NU 9056 inhibited cell proliferation, arrested cell cycle in the G2/M phase, and induced apoptosis through the stimulation of ER stress, thus inhibiting the JAK2/STAT3 signalling pathway and regulating MAPK pathways in ENKTL cells.

scholarly journals Expression of CD70 in nasal natural killer/T cell lymphoma cell lines and patients; its role for cell proliferation through binding to soluble CD27

2012 ◽  
Vol 160 (3) ◽  
pp. 331-342 ◽  
Author(s):  
Kazumi Yoshino ◽  
Kan Kishibe ◽  
Toshihiro Nagato ◽  
Seigo Ueda ◽  
Yuki Komabayashi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Natural Killer ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Lymphoma Cell ◽  
Natural Killer T Cell ◽  
Killer T Cell ◽  
Natural Killer T

Natural killer T-cell lymphoma causing bilateral recurrent recalcitrant dacryocystitis

Orbit ◽  
2021 ◽  
pp. 1-5
Author(s):  
Elzbieta Mechel ◽  
Ann. Q. Tran ◽  
Victoria S. North ◽  
Farnoush M. Moen ◽  
Andrea A. Tooley
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Natural Killer T Cell ◽  
Killer T Cell ◽  
Natural Killer T

scholarly journals Daratumumab monotherapy for patients with relapsed or refractory natural killer/T-cell lymphoma, nasal type: an open-label, single-arm, multicenter, phase 2 study

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Huiqiang Huang ◽  
Jun Zhu ◽  
Ming Yao ◽  
Tae Min Kim ◽  
Dok Hyun Yoon ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Phase 2 ◽  
Nasal Type ◽  
Natural Killer T Cell ◽  
Phase 2 Study ◽  
Duration Of Response ◽  
Killer T Cell

Abstract Background Natural killer/T-cell lymphoma (NKTCL) is a disease with limited treatment options and poor outcomes. Daratumumab monotherapy demonstrated clinical activity in a single-patient case report. We present data from the primary analysis of a phase 2 study of daratumumab monotherapy in relapsed or refractory (R/R) NKTCL. Methods This phase 2 study with Simon’s two-stage design evaluated daratumumab in patients with histologically confirmed extranodal NKTCL, nasal type, per WHO classification that was refractory to or relapsed after ≥ 1 line of chemotherapy, who were not candidates for other treatment modalities. All patients received daratumumab 16 mg/kg intravenously once weekly for Cycles 1 and 2, every other week for Cycles 3 through 6, and every 4 weeks thereafter until progression or unacceptable toxicity; all cycles were 28 days. The primary end point was objective response rate (ORR) based on blinded independent central review per Revised Criteria for Response Assessment of Hodgkin and non-Hodgkin Lymphoma (Lugano classification). Results In total, 32 Asian patients received daratumumab. The ORR was 25.0% (95% confidence interval [CI] 11.5–43.4); all 8 responders had a partial response; and the median duration of response was 55.0 days (95% CI 29–339). At 10.2 months of median follow-up, median progression-free survival (PFS) was 53.0 days (95% CI 43–106); the 4-month PFS rate was 13.0%. Median overall survival (OS) was 141.0 days (95% CI 94–438); the 6-month OS rate was 42.9%. Nineteen (59.4%) patients had grade 3/4 treatment-emergent adverse events (TEAEs); the most common was thrombocytopenia (25.0%; n = 8). TEAEs leading to death occurred in 4 patients (death, respiratory failure, septic shock, and pneumonia); all were unrelated to daratumumab. Conclusions In patients with R/R NKTCL, daratumumab monotherapy was well tolerated with no new safety concerns and achieved an ORR of 25.0%. However, no patients achieved complete response, and duration of response was short. Trial registration ClinicalTrials.gov, NCT02927925. Registered 7 October 2016.

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