scholarly journals Differential Effects of Reactive Oxygen Species on IgG versus IgM Levels in TLR-Stimulated B Cells

2020 ◽  
Vol 204 (8) ◽  
pp. 2133-2142 ◽  
Author(s):  
Karin Margaretha Gilljam ◽  
Kristine Lillebø Holm ◽  
Muhammad Zahoor ◽  
Federica Grazia Centonze ◽  
Hesso Farhan ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
B Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Differential Effects

scholarly journals Radiation therapy-induced reactive oxygen species specifically eliminates CD19+ IgA+ B cells in nasopharyngeal carcinoma

2019 ◽  
Vol Volume 11 ◽  
pp. 6299-6309 ◽  
Author(s):  
Weiwei Li ◽  
Luman Wang ◽  
Chunying Shen ◽  
Tingting Xu ◽  
Yiwei Chu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Radiation Therapy ◽  
B Cells ◽  
Nasopharyngeal Carcinoma ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals Differential effects of Bcl-2 and caspases on mitochondrial permeabilization during endogenous or exogenous reactive oxygen species-induced cell death

2012 ◽  
Vol 28 (4) ◽  
pp. 239-253 ◽  
Author(s):  
Vincent Rincheval ◽  
Marie Bergeaud ◽  
Lise Mathieu ◽  
Jacqueline Leroy ◽  
Arnaud Guillaume ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Differential Effects ◽  
Mitochondrial Permeabilization

Green Tea Component, Catechin, Induces Apoptosis of Human Malignant B Cells via Production of Reactive Oxygen Species

2005 ◽  
Vol 11 (16) ◽  
pp. 6040-6049 ◽  
Author(s):  
Tomonori Nakazato ◽  
Keisuke Ito ◽  
Yasuo Ikeda ◽  
Masahiro Kizaki
Keyword(s):  
Reactive Oxygen Species ◽  
B Cells ◽  
Green Tea ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals Ibrutinib Selects for Cells with Elevated Reactive Oxygen Species and Downregulated Phosphatases

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3795-3795
Author(s):  
Nathan Camp ◽  
Meghan Garrett ◽  
Ajay K. Gopal ◽  
Richard James
Keyword(s):  
Reactive Oxygen Species ◽  
B Cells ◽  
B Cell ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Oxygen Species

Signals from the B-cell receptor are inappropriately activated in B-cell malignancies, including Chronic lymphocytic leukemia (CLL), Mantle cell lymphoma (MCL), and Diffuse large B-cell lymphoma (DLBCL). In CLL, 90% of patients respond to treatment with ibrutinib, an inhibitor of Bruton's Tyrosine Kinase (BTK), with a mean three-year progression free survival rate of approximately 60%. Despite these promising numbers, patients who do not initially respond to ibrutinib have extremely poor outcomes, and nearly all patients eventually become resistant to ibrutinib due to mutations in BTK and its downstream effector Phospholipase C gamma 2 (PLCG2), with a median survival time of 23 months. In order to identify salvage therapies for ibrutinib-resistant patients, we employed several quantitative proteomic methods to identify signaling pathways and proteins that are essential in ibrutinib-resistant patient cells and cell lines. Total proteomic analysis of lymphoma cell lines selected with ibrutinib in vitro revealed that multiple mitochondrial proteins are increased in B cells exposed to ibrutinib. Next, we found that ibrutinib-treated B cells also exhibited increases in reactive oxygen species (ROS), which potently inhibit several protein phosphatases, including B cell receptor signaling regulators PTPN6 and INPP5D. We next looked at tyrosine phosphorylation in patient B cells collected at several time points during ibrutinib treatment and found decreased phosphorylation of both PTPN6 (Y536) and INPP5D (Y944 and Y865) during treatment. Furthermore, total levels of PTPN6 are decreased in patients within 3 months of initiating treatment, and disruption of PTPN6 in cell lines by CRISPR provided a selective advantage in ibrutinib-treated cell populations. Finally, we found that ibrutinib-treated and ibrutinib-naïve primary CLL cells are sensitive to compounds that prevent reactive oxygen species generation (SOD and PHOX inhibitors). Combined, we propose a mechanism by which ibrutinib treatment leads to increased levels of ROS and decreased phosphatase activity, ultimately leading to a growth advantage in the presence of ibrutinib without concomitant mutations in PLCG2 and BTK. We hypothesize that targeting proteins important for reactive oxygen species generation would also be useful in patients and could result in regained disease control and/or prevention of acquired resistance. Disclosures Gopal: Seattle Genetics, Pfizer, Janssen, Gilead, Sanofi, Spectrum, Amgen, Aptevo, BRIM bio, Acerta, I-Mab-pharma, Takeda, Compliment, Asana Bio, and Incyte.: Consultancy; Teva, Bristol-Myers Squibb, Merck, Takeda, Seattle Genetics, Pfizer, Janssen, Takeda, and Effector: Research Funding; Seattle Genetics, Pfizer, Janssen, Gilead, Sanofi, Spectrum, Amgen, Aptevo, BRIM bio, Acerta, I-Mab-pharma, Takeda, Compliment, Asana Bio, and Incyte: Honoraria.

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