Addiction of primary cutaneous γδ T cell lymphomas to JAK/STAT signaling
Yue Zhang, … , Naiem T. Issa, Jaehyuk Choi
Yue Zhang, … , Naiem T. Issa, Jaehyuk Choi
Published April 15, 2025
Citation Information: J Clin Invest. 2025;135(8):e180417. https://doi.org/10.1172/JCI180417.
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Research Letter Dermatology Oncology

Addiction of primary cutaneous γδ T cell lymphomas to JAK/STAT signaling

Abstract

Authors

Yue Zhang, Julia A. Yescas, Kristy Tefft, Spencer Ng, Kevin Qiu, Erica B. Wang, Shifa Akhtar, Addie Walker, Macartney Welborn, Martin Zaiac, Joan Guitart, Aamir M. Qureshi, Youn H. Kim, Michael S. Khodadoust, Naiem T. Issa, Jaehyuk Choi

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Figure 1

PCGDTL regression with JAK inhibitor monotherapy and mechanisms of acquired resistance.

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PCGDTL regression with JAK inhibitor monotherapy and mechanisms of acqui...
(A) Clinical response of patient 1 to ruxolitinib. (B) WGS of PCGDTL in patient 1 revealed a deletion in p13.13, containing the SOCS1 locus. CN, copy number; LRR, log R ratio. (C) GSEA of Hallmark IL-2/STAT5 signaling of 2 tumor samples against 3 normal mature Vδ1 T cells revealed increased activity. (D) The post-relapse PCGDTL contained an acquired STAT5B p.N642H mutation. (E) STAT5B p.N642H increased the IC50 of ruxolitinib in SOCS1-deficient Ba/F3 cells. (F) Clinical response of patient 2 to cerdulatinib. (G) NGS of PCGDTL in patient 2 revealed a JAK3 p.A573V mutation and a post-relapse JAK3 p.M511I mutation. (H) GSEA of Hallmark IL-2/STAT5 signaling of 3 tumor samples against 3 normal mature Vδ1 T cells revealed increased activity. (I) Post-relapse leukemic PCGDTL contained an additional JAK1 p.L783F and subclonal JAK1 p.T901A mutations. (J) JAK3 p.M511I and JAK1 p.L783F increased the IC50 of cerdulatinib in Ba/F3 cells containing JAK3 p.A573V in the absence of IL-3. ****P < 0.0001, by multiple-comparison 2-way ANOVA (E and J). Created with BioRender.com.