Repression of TCF3/E2A contributes to Hodgkin lymphomagenesis

This is the authors' abstract. We don't add key points for this paper.

// Hanfeng Guan 1, 2 , Linka Xie 3 , Thomas Wirth 2 , Alexey Ushmorov 2 1 Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 2 Institute of Physiological Chemistry, University of Ulm, Ulm, Germany 3 Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China Correspondence to: Linka Xie, e-mail: xlk00200@hotmail.com Alexey Ushmorov, e-mail: alexey.ushmorov@uni-ulm.de Keywords: classical Hodgkin lymphoma (cHL), TCF3/E2A, cell death Received: April 22, 2015 Accepted: April 25, 2016 Published: May 6, 2016 ABSTRACT Although Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) derived from germinal or post germinal B cells, they have lost the B cell phenotype in the process of lymphomagenesis. The phenomenon can be at least partially explained by repression of B-cell-specific transcription factors including TCF3, early B-cell factor 1 (EBF1), SPI1/PU.1, and FOXO1, which are down-regulated by genetic and epigenetic mechanisms. The unique phenotype has been suspected to be advantageous for survival of HRS cells. Ectopic expression of some of these transcription factors (EBF1, PU.1, FOXO1) indeed impaired survival of cHL cells. Here we show that forced expression of TCF3 causes cell death and cell cycle arrest in cHL cell lines. Mechanistically, TCF3 overexpression modulated expression of multiple pro-apoptotic genes including BIK, APAF1, FASLG, BOK, and TNFRSF10A/DR4. We conclude that TCF3 inactivation contributes not only to extinguishing of B cell phenotype but also to cHL oncogenesis.