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

Chung, Elaine Y. L.; Sartori, Giulio; Ponzoni, Maurilio; Cascione, Luciano; Priebe, Valdemar; Xu-Monette, Zijun Y.; Fang, Xiaosheng; Zhang, Mingzhi; Visco, Carlo; Tzankov, Alexandar; Rinaldi, Andrea; Sgrignani, Jacopo; Zucca, Emanuele; Rossi, Davide; Cavalli, Andrea; Inghirami, Giorgio; Scott, David W.; Young, Ken H.; Bertoni, Francesco

doi:10.1111/bjh.19018

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Bertoni_2023_Wiley_Brit J Haematol_ETS1 phosphorylation

Journal article

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

Chung, Elaine Y. L. Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Sartori, Giulio Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Ponzoni, Maurilio ORCID IRCCS San Raffaele Hospital Scientific Institute, Vita Salute San Raffaele University, Milan, Italy
Cascione, Luciano Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland
Priebe, Valdemar Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Xu-Monette, Zijun Y. Duke University Medical Center, Durham, North Carolina, USA
Fang, Xiaosheng ORCID Duke University Medical Center, Durham, North Carolina, USA
Zhang, Mingzhi Duke University Medical Center, Durham, North Carolina, USA
Visco, Carlo Section of Hematology, Department of Medicine, University of Verona, Verona, Italy
Tzankov, Alexandar ORCID Pathology, Institute of Medical Genetics and Pathology, University Hospital, Basel, Switzerland
Rinaldi, Andrea Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Sgrignani, Jacopo ORCID Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Zucca, Emanuele ORCID Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
Rossi, Davide Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
Cavalli, Andrea ORCID Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Inghirami, Giorgio Pathology and Laboratory Medicine Department, Weill Cornell Medicine, New York, New York, USA
Scott, David W. Centre for Lymphoid Cancer, BC Cancer, University of British Columbia, Vancouver, British Columbia, Canada - Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
Young, Ken H. Duke University Medical Center, Durham, North Carolina, USA
Bertoni, Francesco ORCID Institute of Oncology Research (IOR), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland

2023

Published in:

British journal of haematology. - 2023, vol. 203, no. 2, p. 244-254

Diffuse large B-cell lymphoma (DLBCL)

English 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.

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