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

被引：0

作者：

Chung, Elaine Y. L. ^{[1
]}

Sartori, Giulio ^{[1
]}

Ponzoni, Maurilio ^{[2
]}

Cascione, Luciano ^{[1
,3
]}

Priebe, Valdemar ^{[1
]}

Xu-Monette, Zijun Y. ^{[4
]}

Fang, Xiaosheng ^{[4
]}

Zhang, Mingzhi ^{[4
]}

Visco, Carlo ^{[5
]}

Tzankov, Alexandar ^{[6
]}

Rinaldi, Andrea ^{[1
]}

Sgrignani, Jacopo ^{[7
]}

Zucca, Emanuele ^{[8
]}

Rossi, Davide ^{[1
,8
]}

Cavalli, Andrea ^{[7
]}

Inghirami, Giorgio ^{[9
]}

Scott, David W. W. ^{[10
,11
]}

Young, Ken H. H. ^{[4
]}

Bertoni, Francesco ^{[1
,8
,12
]}

机构：

[1] USI, Inst Oncol Res, Fac Biomed Sci, Bellinzona, Switzerland

[2] Univ Vita Salute San Raffaele, IRCCS San Raffaele Hosp Sci Inst, Milan, Italy

[3] SIB Swiss Inst Bioinformat, Lausanne, Switzerland

[4] Duke Univ, Med Ctr, Durham, NC USA

[5] Univ Verona, Dept Med, Sect Hematol, Verona, Italy

[6] Univ Hosp, Inst Med Genet & Pathol, Pathol, Basel, Switzerland

[7] USI, Inst Res Biomed, Fac Biomed Sci, Bellinzona, Switzerland

[8] Ente Osped Cantonale, Oncol Inst Southern Switzerland, Bellinzona, Switzerland

[9] Weill Cornell Med, Pathol & Lab Med Dept, New York, NY USA

[10] Univ British Columbia, Ctr Lymphoid Canc, BC Canc, Vancouver, BC, Canada

[11] Univ British Columbia, Dept Med, Vancouver, BC, Canada

[12] Inst Oncol Res, Via Francesco Chiesa 5, CH-6500 Bellinzona, Switzerland

来源：

BRITISH JOURNAL OF HAEMATOLOGY | 2023年 / 203卷 / 02期

关键词：

11q24.3; gain; diffuse large B-cell lymphoma (DLBCL); ETS1; Thr38; phosphorylation; MEK/ERK axis; ENRICHMENT ANALYSIS; DOMAIN; SIGNATURES; PACKAGE;

D O I：

10.1111/bjh.19018

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：244 / 254

页数：11

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