Abstract
Angioimmunoblastic T-cell lymphoma (AITL) is one of the most common subtypes of peripheral T-cell lymphoma. Advances in understanding the mutational landscape of AITL have not resulted in improved prognosis nor consensus regarding optimal first-line and second-line treatment.The recently proposed multistep tumorigenesis model for AITL provides a theoretical framework of AITL oncogenesis. In this model, early mutations in epigenetic modifiers interact with late cooperative mutations to enable malignant transformation. Frequent mutations in epigenetic modifiers suggest that aberrant DNA methylation contributes to AITL oncogenesis. Several research groups have reported findings suggesting that inappropriate costimulation acts as a late cooperative mutation. Drugs targeting inappropriate costimulation have already been approved for the treatment of several malignancies or autoimmune diseases. Additionally, aberrant DNA methylation was recently shown to potentiate inappropriate costimulation in a subset of AITL cases. Therefore, drugs targeting inappropriate costimulation and hypomethylating agents might have synergistic effects. Both offer promising new therapeutic options in AITL treatment.This commentary summarizes the main findings on aberrant DNA methylation and inappropriate costimulation in AITL and proposes several already approved drugs for AITL treatment. Hopefully, these will contribute to improving the still dismal prognosis of AITL patients.
Highlights
Peripheral T-cell lymphoma (PTCL) constitutes a heterogeneous group of non-Hodgkin lymphomas generally characterized by an aggressive clinical course and poor prognosis [1]
Together with the fact that aberrant DNA methylation contributes to Angioimmunoblastic T-cell lymphoma (AITL) oncogenesis, these findings provide a strong biological and theoretical rationale for the simultaneous use of hypomethylating agents and drugs targeting inappropriate costimulation in mutant Isocitrate dehydrogenase 2 (IDH2) AITL cases with mutations in costimulatory pathways
Advances in understanding the mutational landscape of AITL have not resulted in improved prognosis nor consensus regarding optimal first-line and second-line treatment
Summary
Peripheral T-cell lymphoma (PTCL) constitutes a heterogeneous group of non-Hodgkin lymphomas generally characterized by an aggressive clinical course and poor prognosis [1]. As the evidence suggests that hypermethylation and subsequent downregulation of PTPN7, SIT1 and DGKα can potentially increase signaling through the Ras/Raf/MAPK/ ERK pathway, it is possible that these epigenetic changes contribute to deregulated T cell activation and AITL oncogenesis.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
