New insights into the pathogenesis and molecular understanding of cutaneous T-cell lymphomas

Abstract

The pathogenesis of cutaneous T‑cell lymphomas (CTCL) is still an enigma. Therefore, extensive translational research efforts have been undertaken in recent years to gain further clinical and molecular insights. There is increasing evidence that the different clinical appearance of the CTCL subtypes derives from the assumption that they develop from different skin subpopulations of Tcells. Detection and quantification of the malignant T‑cell clones is crucial for the diagnosis and prognosis of CTCL. Numerous recurrent mutant cellular signalling pathways have been found in recent years. This includes the JAK-STAT, NFκB, T‑cell receptor and MAP kinase signalling pathways, as well as cell cycle control and epigenetics. The most recent analyses imply atumour evolution model with initial copy number variation, like amplification or deletions of specific DNA fragments (CNVs) and only subsequent later single nucleotide variations (SNVs). The crucial question, however, is which CNVs are sufficient to initiate general tumourigenesis? The challenge is to identify possible driver genes. Increasing molecular understanding in CTCL will include new breakthrough therapeutic options in the near future.