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.
Elaine Y L ChungGiulio SartoriMaurilio PonzoniLuciano CascioneValdemar PriebeZijun Y Xu-MonetteXiaosheng FangMingzhi ZhangChiara RusconiAlexandar TzankovAndrea RinaldiJacopo SgrignaniEmanuele ZuccaDavide RossiAndrea CavalliGiorgio InghiramiDavid W ScottKen H YoungFrancesco BertoniPublished in: British journal of haematology (2023)
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.
Keyphrases
- diffuse large b cell lymphoma
- transcription factor
- protein kinase
- epstein barr virus
- induced apoptosis
- end stage renal disease
- gene expression
- single cell
- cell cycle arrest
- chronic kidney disease
- newly diagnosed
- genome wide
- dna methylation
- electronic health record
- endoplasmic reticulum stress
- machine learning
- mesenchymal stem cells
- prognostic factors
- endothelial cells
- rna seq
- cell death
- heat stress