Caspase 10 (Mch4/FLICE2) is a caspase homologous to caspase 8. A recent report described that inherited CASP10 gene mutations underlie defective lymphocyte and dendritic cell apoptosis in autoimmune lymphoproliferative syndrome (ALPS). In this study, to explore the possibility that mutation of this gene might be involved in the development of non-Hodgkin lymphoma (NHL), we have analyzed the entire coding region and all splice sites of the CASP10 gene for the detection of somatic mutations in 117 human NHLs. Overall, 17 NHLs (14.5%) were found to have CASP10 mutations, which were identified in the coding regions of the prodomain (n = 3), the p17 large protease subunit (n = 11), and the p12 small protease subunit (n = 3). We expressed the tumor-derived caspase 10 mutants in 293 cells and found that apoptosis was suppressed. These data suggest that the inactivating mutations of the CASP10 gene might lead to the loss of its apoptotic function and contribute to the pathogenesis of some human NHLs.
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http://dx.doi.org/10.1182/blood.v99.11.4094 | DOI Listing |
Oncology
December 2024
Department of Respiratory and Critical Care Medicine, Shanghai Pudong Hospital, Shanghai, China.
Introduction: The incidence of lung cancer remains high worldwide and is still the leading cause of cancer-related deaths globally. The primary reason for this is that the vast majority of patients are diagnosed only when the disease has progressed to an advanced stage or metastasized. Therefore, early diagnosis of lung cancer is crucial.
View Article and Find Full Text PDFCurr Med Chem
October 2024
Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, Guangxi Zhuang Autonomous Region, 530031, China.
Immunol Res
August 2024
Department of Pediatric Health and Diseases, Department of Pediatric Immunology, Faculty of Medicine, Ege University, Izmir, Turkey.
Human Inborn Errors of Immunity (IEIs) encompass a clinically and genetically heterogeneous group of disorders, ranging from mild cases to severe, life-threatening types. Among these, Primary Immune Regulatory Disorders (PIRDs) constitute a subset of IEIs characterized by diverse clinical phenotypes, prominently featuring severe atopy, autoimmunity, lymphoproliferation, hyperinflammation, autoinflammation, and susceptibility to malignancies. According to the latest report from the International Union of Immunological Societies (IUIS), PIRDs arise from mutations in various genes including LYST, RAB27A, AP3B1, AP3D1, PRF1, UNC13D, STX11, STXBP2, FAAP24, SLC7A7, RASGRP1, CD70, CTPS1, RLTPR, ITK, MAGT1, PRKCD, TNFRSF9, SH2DIA, XIAP, CD27 (TNFRSF7), FAS (TNFRSF6), FASLG (TNFSF6), CASP10, CASP8, FADD, LRBA, STAT3, AIRE, ITCH, ZAP70, TPP2, JAK1, PEPD, FOXP3, IL2RA, CTLA4, BACH2, IL2RB, DEF6, FERMT1, IL10, IL10RA, IL10RB, NFAT5, TGFB1, and RIPK1 genes.
View Article and Find Full Text PDFArch Toxicol
June 2024
Institute of Sport Science, University of the Bundeswehr Munich, Werner-Heisenberg-Weg 39, 85577, Neubiberg, Germany.
Poisoning with the organophosphorus nerve agent VX can be life-threatening due to limitations of the standard therapy with atropine and oximes. To date, the underlying pathomechanism of VX affecting the neuromuscular junction has not been fully elucidated structurally. Results of recent studies investigating the effects of VX were obtained from cells of animal origin or immortalized cell lines limiting their translation to humans.
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