Fig. 4

Concurrent genetic mutations of TET2^MT PTCL. A. RHOA^G17V mutation and mutations of key components of TCR and ICOS signaling pathways such as CD28, PLCG1, and VAV1 commonly co-occur in TET^MT PTCL. Consequently, TCR and ICOS signaling are activated in TET2^MT PTCL, determining the Tfh phenotype. In addition, second TET2 mutations are commonly detected in TET2^MT PTCL. Moreover, IDH2^R172K mutation also commonly co-occurs in TET2^MT PTCL. B. The molecular mechanism of RHOA^G17V mutation in the pathogenesis of PTCL in collaboration with TET2^MT. RHOA^G17V mutation antagonizes the normal function of RHOA and activates ICOS-AKT-mTOR and PLCγ1-NFAT signaling by stimulating the activation of VAV1. TET2^MT collaborates with RHOA^G17V mutation in the regulation of FoxO1 activity in T-cells. (Created with BioRender.com)