Abstract

<p>Peripheral T-cell lymphomas (PTCLs) encompass a diverse group of aggressive non-Hodgkin��s lymphomas originating from mature T lymphocytes. Despite their relatively low prevalence compared to B-cell lymphomas, PTCLs pose significant clinical challenges due to their heterogeneity, lack of specific biomarkers, and often poor response to conventional chemotherapies. Unraveling the intricate pathogenic mechanisms underlying PTCLs is pivotal for the development of targeted therapies, which has become a major focus of PTCL research in recent years. It was previously postulated that genomic alterations play a pivotal role in T-cell transformation and lymphomagenesis. Recent multi-omics investigations and functional studies focusing on pathogenic mechanisms have unveiled that in addition to genetic abnormalities, diverse intrinsic and extrinsic mechanisms are implicated in the pathogenesis of PTCLs. In this Review, we provide an overview of the recent advances in the pathogenesis and management of PTCLs, focusing on the current and potential precise diagnosis and treatment based on intrinsic and extrinsic mechanisms. Bioengineering and drug development have enabled the effective modulation of many previously ��undruggable�� targets, which offers the potential to target new biomarkers associated with PTCL pathogenesis. The integration of artificial intelligence (AI) in clinical practice enables a comprehensive framework, merging diverse data sources and clinical context to discover precise biomarkers for personalized medicine. Finally, we present pressing questions and challenges that demand attention and discuss emerging solutions.</p>

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