In the present study, we searched selective cytotoxicity and mitochondria mediated apoptosis of novel COX-2 inhibitor 2-(4-(Methylsulfonyl)phenyl)imidazo[1,2-] pyridine-8-carboxylic acid on B-lymphocytes and their mitochondria isolated from normal subjects and acute lymphoblastic leukemia (ALL) patients' blood. Our results showed this compound can selectively induce cellular and mitochondrial toxicity on ALL B-lymphocytes and mitochondria without any toxic effects on normal B-lymphocytes and their mitochondria. Taken together, the results of this study suggest that cancerous mitochondria are a potential target for the ALL B-lymphocytes. Selective toxicity of COX-2 inhibitor in cancerous mitochondria could be an attractive therapeutic option for the effective clinical management of therapy-resistant ALL.
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http://dx.doi.org/10.1080/07357907.2020.1808898 | DOI Listing |
Nat Commun
December 2024
Department of Rheumatology and Clinical Immunology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Upon activation, naive B cells exit their quiescent state and enter germinal center (GC) responses, a transition accompanied by increased protein synthesis. How protein translation efficiency is adequately adjusted to meet the increased demand requires further investigation. Here, we identify the methyltransferase METTL1 as a translational checkpoint during GC responses.
View Article and Find Full Text PDFNat Commun
December 2024
Immunity and Cancer Laboratory, Francis Crick Institute, London, UK.
To increase antibody affinity against pathogens, positively selected GC-B cells initiate cell division in the light zone (LZ) of germinal centers (GCs). Among these, higher-affinity clones migrate to the dark zone (DZ) and vigorously proliferate by utilizing energy provided by oxidative phosphorylation (OXPHOS). However, it remains unknown how positively selected GC-B cells adapt their metabolism for cell division in the glycolysis-dominant, cell cycle arrest-inducing, hypoxic LZ microenvironment.
View Article and Find Full Text PDFNat Commun
November 2024
Division of Rheumatology, Department of Medicine, Mayo Clinic Rochester, Rochester, MN, USA.
Germinal center (GC) formation, which is an integrant part of humoral immunity, involves energy-consuming metabolic reprogramming. Rag-GTPases are known to signal amino acid availability to cellular pathways that regulate nutrient distribution such as the mechanistic target of rapamycin complex 1 (mTORC1) pathway and the transcription factors TFEB and TFE3. However, the contribution of these factors to humoral immunity remains undefined.
View Article and Find Full Text PDFDokl Biochem Biophys
October 2024
Kazan State Medical University, Kazan, Russia.
Chronic lymphocytic leukemia is a hemoblastosis of CD5 B lymphocytes with lymphocytosis, damage to the lymphatic organs, occurring in the older age group, the etiology and pathogenesis of which are not fully understood. Oxidative stress is an important factor in the regulation of stem cells and the activation of intracellular survival signaling pathways in chronic lymphocytic leukemia cells. The aim of the study was to analyze the current data on the role of redox status changes in the pathogenesis of chronic lymphocytic leukemia.
View Article and Find Full Text PDFJ Immunol Res
October 2024
Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, Jiangsu, China.
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