<p>Primary cutaneous γδ T-cell lymphoma (PCGDTL) is a mature T-cell lymphoma (TCL) of the skin with a median survival of 31 months and no effective therapies. PCGDTLs frequently possess mutations in the JAK/STAT pathway, including in <a href="https://www.ncbi.nlm.nih.gov/gene/3716">JAK1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/3718">JAK3</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/6774">STAT3</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/6777">STAT5B</a>, and <a href="https://www.ncbi.nlm.nih.gov/gene/8651">SOCS1</a>. We hypothesized that single-agent JAK inhibition may be effective in PCGDTLs, particularly those with targetable JAK/STAT pathway mutations. Herein, we demonstrate the near-complete response of two PCGDTL cases to single-agent JAK inhibitors, ruxolitinib or cerdulatinib. However, both patients eventually relapsed with acquired mutations in JAK1, JAK3, or STAT5B.</p>

Addiction of Primary Cutaneous Gamma-Delta T-cell Lymphomas to JAK-STAT Signaling