ETS1在苏氨酸38位点的磷酸化与弥漫大B细胞淋巴瘤的起源细胞相关，并支持肿瘤细胞的生长。
ETS1 phosphorylation at threonine 38 is associated with the cell of origin of diffuse large B cell lymphoma and sustains the growth of tumour cells.
发表日期：2023 Aug 16
作者：
Elaine Y L Chung, Giulio Sartori, Maurilio Ponzoni, Luciano Cascione, Valdemar Priebe, Zijun Y Xu-Monette, Xiaosheng Fang, Mingzhi Zhang, Carlo Visco, Alexandar Tzankov, Andrea Rinaldi, Jacopo Sgrignani, Emanuele Zucca, Davide Rossi, Andrea Cavalli, Giorgio Inghirami, David W Scott, Ken H Young, Francesco Bertoni
来源：
BIOMEDICINE & PHARMACOTHERAPY
摘要：
转录因子ETS1在25%的弥漫性大B细胞淋巴瘤(DLBCL)中上调。我们在这里研究了ETS1苏氨酸38磷酸化在DLBCL细胞模型和临床样本中的作用。在激活的B细胞型DLBCL (ABC)中检测到p-ETS1，而在生发中心B细胞型DLBCL (GCB)细胞系中未检测到，相应地，在ABC DLBCL诊断活检中，p-ETS1较GCB DLBCL更为常见。MEK抑制既降低了基线水平，也降低了IgM刺激诱导的p-ETS1水平。在DLBCL细胞系中，ETS1苏氨酸38磷酸化的遗传抑制影响了细胞生长和BCR介导的转录组程序。我们的数据表明，ETS1苏氨酸38磷酸化对DLBCL细胞的生长很重要，其药物抑制可能有益于淋巴瘤患者。© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.
The transcriptional factor ETS1 is upregulated in 25% of diffuse large B cell lymphoma (DLBCL). Here, we studied the role of ETS1 phosphorylation at threonine 38, a marker for ETS1 activation, in DLBCL cellular models and clinical specimens. p-ETS1 was detected in activated B cell-like DLBCL (ABC), not in germinal centre B-cell-like DLBCL (GCB) cell lines and, accordingly, it was more common in ABC than GCB DLBCL diagnostic biopsies. MEK inhibition decreased both baseline and IgM stimulation-induced p-ETS1 levels. Genetic inhibition of phosphorylation of ETS1 at threonine 38 affected the growth and the BCR-mediated transcriptome program in DLBCL cell lines. Our data demonstrate that ETS1 phosphorylation at threonine 38 is important for the growth of DLBCL cells and its pharmacological inhibition could benefit lymphoma patients.© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.