Identifying Genes Associated With Proliferation, Immunity and Thrombosis in Paroxysmal Nocturnal Haemoglobinuria.

Autor: Du Y; Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Wang D; Medical Zhongcheng Limited Company, Hangzhou, China., Hu Q; Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Lai Z; Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China., Yang C; Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., He H; Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Wang S; Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Zhang H; Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China., Chen P; Department of Hematology, the Seventh Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China., Li Z; Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Chen M; Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China., Han B; Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2024 Dec; Vol. 28 (23), pp. e70295.
DOI: 10.1111/jcmm.70295
Abstrakt: PIGA mutation cannot fully explain the proliferative advantage of abnormal clones and thrombosis tendency in paroxysmal nocturnal haemoglobinuria (PNH), and additional genes may play a role, justifying further investigation. CD59+ and CD59- peripheral blood mononuclear cells from six PNH patients were sorted and subjected to whole-exon sequencing (WES) and whole-transcriptome sequencing respectively. Six age- and sex-matched healthy volunteers were enrolled as controls. Genes related to proliferation, immunity and thrombosis were selected by gene ontology (GO) analysis. The selected gene mutant alleles were then identified in the WES results for 40 patients and verified by the Sanger method in another 40 PNH patients. CD59+ and CD59- peripheral blood mononuclear cells from seven patients were sorted, and the RNA and protein expression levels of target genes were assessed via quantitative real-time PCR (RT-qPCR), flow cytometry and western blotting. The final selected genes were then related to clinical features to analyse. T-cell activation-related genes were upregulated, whereas platelet degranulation, coagulation, haemostasis, leukocyte proliferation and platelet activation-related genes were downregulated in both CD59+ and CD59- cells. The mRNA or protein expression levels of SELP, FLT1, NRP1 and vWF were either different from those in healthy controls or different between CD59+ and CD59- cells. Moreover, platelet aggregation was greater in patients with mutations in these genes than in patients without such mutations. Except for PIGA, other genes may be involved in the proliferation and coagulopathy that occur in PNH patients.
(© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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