Mycosis fungoides and Sezary syndrome

Mycosis fungoides (MF) and the Sezary syndrome (SS) remain hematological T-cell lymphoproliferations of poor prognosis. However our knowledge of these diseases has increased significantly in recent years. First, their normal cellular counterparts have been identified; central-memory T cells for SS, while MF cells have a phenotype of memory-effector T cells. The genomic studies have shown that hypermethylation correlated with the aggressiveness of the disease. The microarray studies have identified gene expression profiles not truly specific for MF or SS, but that are able to partially predict the effectiveness of drugs such as interferon or vorinostat. Moreover, these microarray studies have helped to highlight the activation of oncogenic pathways, suggesting to consider novel therapeutic approaches. This last point is most problematic in the MF/SS since many new molecules and new indications have been proposed (histone deacetylase inhibitors, proteasome inhibitors, new anti-folate, monoclonal antibodies), but no drug, at least in monotherapy, has so far proven to be highly effective in the severe forms of MF/SS.