التفاصيل البيبلوغرافية
| العنوان: |
A novel function of STAT3β in suppressing interferon response improves outcome in acute myeloid leukemia |
| المؤلفون: |
Sophie Edtmayer, Agnieszka Witalisz-Siepracka, Bernhard Zdársky, Kerstin Heindl, Stefanie Weiss, Thomas Eder, Sayantanee Dutta, Uwe Graichen, Sascha Klee, Omar Sharif, Rotraud Wieser, Balázs Győrffy, Valeria Poli, Emilio Casanova, Heinz Sill, Florian Grebien, Dagmar Stoiber |
| المصدر: |
Cell Death and Disease, Vol 15, Iss 5, Pp 1-12 (2024) |
| بيانات النشر: |
Nature Publishing Group, 2024. |
| سنة النشر: |
2024 |
| المجموعة: |
LCC:Cytology |
| مصطلحات موضوعية: |
Cytology, QH573-671 |
| الوصف: |
Abstract Signal transducer and activator of transcription 3 (STAT3) is frequently overexpressed in patients with acute myeloid leukemia (AML). STAT3 exists in two distinct alternatively spliced isoforms, the full-length isoform STAT3α and the C-terminally truncated isoform STAT3β. While STAT3α is predominantly described as an oncogenic driver, STAT3β has been suggested to act as a tumor suppressor. To elucidate the role of STAT3β in AML, we established a mouse model of STAT3β-deficient, MLL-AF9-driven AML. STAT3β deficiency significantly shortened survival of leukemic mice confirming its role as a tumor suppressor. Furthermore, RNA sequencing revealed enhanced STAT1 expression and interferon (IFN) signaling upon loss of STAT3β. Accordingly, STAT3β-deficient leukemia cells displayed enhanced sensitivity to blockade of IFN signaling through both an IFNAR1 blocking antibody and the JAK1/2 inhibitor Ruxolitinib. Analysis of human AML patient samples confirmed that elevated expression of IFN-inducible genes correlated with poor overall survival and low STAT3β expression. Together, our data corroborate the tumor suppressive role of STAT3β in a mouse model in vivo. Moreover, they provide evidence that its tumor suppressive function is linked to repression of the STAT1-mediated IFN response. These findings suggest that the STAT3β/α mRNA ratio is a significant prognostic marker in AML and holds crucial information for targeted treatment approaches. Patients displaying a low STAT3β/α mRNA ratio and unfavorable prognosis could benefit from therapeutic interventions directed at STAT1/IFN signaling. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2041-4889 |
| Relation: |
https://doaj.org/toc/2041-4889 |
| DOI: |
10.1038/s41419-024-06749-9 |
| URL الوصول: |
https://doaj.org/article/fa3588b01db84ae4a00ac9b61c021e7a |
| رقم الانضمام: |
edsdoj.fa3588b01db84ae4a00ac9b61c021e7a |
| قاعدة البيانات: |
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