RHOA G17V Induces T Follicular Helper Cell Specification and Promotes Lymphomagenesis. Academic Article uri icon

Overview

abstract

  • Angioimmunoblastic T cell lymphoma (AITL) is an aggressive tumor derived from malignant transformation of T follicular helper (Tfh) cells. AITL is characterized by loss-of-function mutations in Ten-Eleven Translocation 2 (TET2) epigenetic tumor suppressor and a highly recurrent mutation (p.Gly17Val) in the RHOA small GTPase. Yet, the specific role of RHOA G17V in AITL remains unknown. Expression of Rhoa G17V in CD4+ T cells induces Tfh cell specification; increased proliferation associated with inducible co-stimulator (ICOS) upregulation and increased phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase signaling. Moreover, RHOA G17V expression together with Tet2 loss resulted in development of AITL in mice. Importantly, Tet2-/-RHOA G17V tumor proliferation in vivo can be inhibited by ICOS/PI3K-specific blockade, supporting a driving role for ICOS signaling in Tfh cell transformation.

publication date

  • February 2, 2018

Research

keywords

  • DNA-Binding Proteins
  • Immunoblastic Lymphadenopathy
  • Mutation
  • Proto-Oncogene Proteins
  • T-Lymphocytes, Helper-Inducer
  • rhoA GTP-Binding Protein

Identity

PubMed Central ID

  • PMC5811310

Scopus Document Identifier

  • 85041589726

Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2018.01.001

PubMed ID

  • 29398449

Additional Document Info

volume

  • 33

issue

  • 2