Biology and Molecular Pathogenesis of Mature T-Cell Lymphomas

Abstract

Peripheral T-cell lymphomas (PTCLs) constitute a highly heterogeneous group of hematological diseases with complex clinical and molecular features consistent with the diversity of the T-cell type from which they originate. In the past several years, the systematic implementation of high-throughput genomic technologies for the analysis of T-cell malignancies has supported an exponential progress in our understanding of the genetic drivers of oncogenesis and unraveled the molecular complexity of these diseases. Recent findings have helped redefine the classification of T-cell malignancies and provided novel biomarkers to improve diagnosis accuracy and analyze the response to therapy. In addition, multiple novel targeted therapies including small-molecule inhibitors, antibody-based approaches, and immunotherapy have shown promising results in early clinical analysis and have the potential to completely change the way T-cell malignancies have been treated traditionally.

Figure 1.

Schematic (A) representation of the RHOA mutations identified in AITL and model for process of malignant transformation leading to AITL (B). (A, Adapted from Palomero et al. 2014, courtesy of Springer/Nature © 2014; B, adapted from Cortés et al. 2018, with permission from Elsevier © 2018.)

Figure 2.

Recurrent mutations and kinase fusions in anaplastic large cell lymphoma (ALCL) converge to induce oncogenic STAT3 activation in ALK⁺ and ALK⁻ ALCL subtypes. (Figure was created from data adapted from Crescenzo et al. 2015.)

Figure 3.

Relevant molecular pathways in PTCL amenable to therapeutic intervention using targeted therapies.