STAT1-mediated interferon signatures are associated with preclinical JAK inhibitor sensitivity in T-ALL

Xu J, Sussman JH, Yang A, Yoshimura S, Hu J, Chen C, Vincent T, Bandyopadhyay S, Li EY, Lim T, Elghawy O, Barsouk A, Karanfilovski D, Wald SL, Chen GM, Wu D, Newman H, Li A, Sun Y, Chen CH, Bernt K, Wood BL, Winter SS, Dunsmore KP, Raetz E, Devidas M, Pounds S, Loh M, Hunger SP, Chiang MY, Diorio C, Di Giacomo D, Pölönen P, Mullighan CG, Yang JJ, Tan K, Teachey DT. STAT1-mediated interferon signatures are associated with preclinical JAK inhibitor sensitivity in T-ALL. Blood. 2025 Jun 5;145(23):2793-2798. doi: 10.1182/blood.2025028566. PMID: 40101143; PMCID: PMC12163734.

We used single-cell genomics to characterize a patient with T-cell acute lymphoblastic leukemia treated in the Children’s Oncology Group AALL0434 trial with poor clinical outcome despite favorable genomic features, identifying a STAT1-mediated interferon-related transcriptional signature and inflammatory microenvironment associated with sensitivity to small-molecule JAK inhibition.