Immunology

Biography

Biography: Madeleine Duvic

Abstract

The Sézary Cell is a puzzling malignant vs activated white blood cell first discovered by dermatologist Albert Sézary. He described the cell with a cerebriform nucleus in patients with erythroderma. Later it was found to be a T-cell by Lutz and others at the NIH and was suspiciously similar to HTLV-1 adult T-cell leukemia although no virus has yet been implicated. Recently, staging has been updated to include blood involvement for patients with SS and the mycosis fungoides form of cutaneous T cell lymphomas. The clinical features of SS are distinct from other forms of CTCL and include erythema > 80%, keratoderma, ectropion, reactive adenopathy, and severe pruritus. The role of staphylococcus and drug induced disease suggests that some patients have persistent antigene stimulation as an initiating factor. Several other clinical Cutaneous T cell lymphomas (CTCL) have been described using clinical features, and histopathologic markers: the CD30 lymphoproliferative disorders, gamma delta lymphomas, subcutaneous panniculitic T cell lymphoma. rnrnrnrn
The molecular basis for MF/SS have been the subject of intense basic research efforts. Genetic studies of the SS cell uncovered genetic instablility with multiple deletions and gains seen by karyotyping and by array CGH. Whole genome sequencing of SS and MF DNA has revealed somatic mutations that may help us to understand what drives the proliferation of the SS cell. Understanding the pathogenesis of the SS cell has translated into new targeted therapies for both SS and MF. These include fusion proteins (denileukindiftitoxin and CD3-diptheria toxin), monoclonal antibodies targeted to CD4, CCR4, CD52, KIRD3L, and CD30. In addition, small molecules such as histone-deacetylase inhibitors have shown sensitivity in SS. Another break through has been in the area of non-ablative allogeneic stem cell transplant that offers cure to a subset of patients. In summary, the future looks bright to finally silence the elusive Sézary cell in the not too distant future.