Frequent and persistent PLCG1 mutations in S ézary cells directly enhance PLCγ1 activity and stimulate NFκB, AP-1 and NFAT signaling. Short title: Gain-of-function PLCG1 mutations in Sézary Syndrome

This study functionally interrogated 9 PLCG1 mutations (p.R48W, p.S312L, p.D342N, p.S345F, p.S520F, p.R1158H, p.E1163K, p.D1165H and the in-frame indel p.VYEEDM1161V) identified in S ézary Syndrome, the leukemic variant of CTCL. The mutations were demonstrated in diagnostic samples and persisted in multiple tumor compartments over time, except in patients who achieved a complete clinical remission. In basal conditions, the majority of the mutations confer PLCγ1 gain-of-functio n activity through increased inositol phosphate production and downstream activation of NFκB, AP-1 and NFAT transcriptional activity.

Source: Journal of Investigative Dermatology - July 30, 2019 Category: Dermatology Authors: Varsha M. Patel, Charlotte E. Flanagan, Marta Martins, Christine L. Jones, Rosie M. Butler, Wesley J. Woollard, Farrah S. Bakr, Antoinette Yoxall, Nelema Begum, Matilda Katan, Sean J. Whittaker, Tracey J. Mitchell Tags: Original Article Source Type: research