Sezary Syndrome : Molecular Genetics
Sezary Syndrome (SS) - Molecular Genetics: SS shows chromosomal instability with complex numeric and structural abnormalities of chromosomes, similar to those in mycosis fungoides. Recurrent balanced translocations are not seen. Genomic alterations in genes involved in cell cycle and epigenetic regulation (ARID1A) and JAK/STAT signaling pathways have been detected. TCR genes are clonally rearranged. There is overexpression of PLS3, DNMT3A (chromatin modifying gene), TWIST1, and EPHA4 and underexpression of STAT4. Recurrent gain-of-function mutations have been detected in genes involved in T-cell receptor signaling, including PLCG1, CD28, and TNFRSF1B. This image of a skin biopsy from a patient with Sezary syndrome shows predominantly large atypical lymphoid cells resembling a large cell lymphoma. This pattern is seen in a minority of cases.