GEO series
A STAT5B-driven mouse model of hepatosplenic γδ T cell lymphoma reveals therapeutic efficacy of JAK inhibitors
GSE271616
Mus musculus; Homo sapiens
Expression profiling by high throughput sequencing
23 samples
Submitted 2026/03/12
Platform GPL24676Platform GPL21103
Summary
Hepatosplenic T cell lymphoma (HSTL) is a rare, aggressive disease primarily affecting young adults. The disease progresses rapidly, with patients displaying low survival rates and poor responses to standard chemotherapy-based treatments. Currently no targeted therapies are available for HSTL, and pre-clinical models to test new treatment options have not been established. Hence, new models recapitulating HSTL are needed. The JAK-STAT signalling pathway is a key pathway dysregulated in HSTL and STAT5B N642H is the most frequent oncogenic mutation. Using a transgenic mouse model, we have previously validated STAT5B N642H as a strong driver of γδ T cell lymphoma. Here, we have established clonal, murine γδ T cell lymphoma cell lines driven by oncogenic STAT5B, which resemble key features of human HSTL. The IL-2 dependent cell line, C15, displays immunophenotypic features as well as commonly dysregulated gene expression profiles shared with patient-derived HSTL cell lines. C15 cells can be engrafted intravenously into immunocompetent mice to generate an aggressive HSTL-like disease. Recipient mice display an expansion of malignant γδ T cells causing hepatosplenomegaly and elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels. Using these models, we tested the potential of JAK inhibition as a targeted treatment strategy for HSTL, with the clinically-approved JAK inhibitor upadacitinib displaying significant anti-tumor efficacy against HSTL cells in vitro and in vivo. Overall, we have developed a robust, accessible and faithful preclinical model of HSTL with the advantage of immune-competence, which can facilitate the study of physiological disease mechanisms and new (immuno)therapy strategies.
Published in
Aung MMK, Schönefeldt S, Pfalz-Kraupp S et al.
· HemaSphere 2026
· PMID 42007450
· doi:10.1002/hem3.70345
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE271616_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 23 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1132296 and SRA study SRP518232. Searching any of these in the dataset finder brings you back here.
Study design
7 conditions, mostly in triplicate
BC ×5
C15 ×3
C2 ×3
C6 ×3
WT_Ly5.2_gd ×3
DERL2 ×3
DERL7 ×3
Supports a between-group comparison across 23 samples.
7 replicated groups read from 23 sample titles; they account for 23 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8380701 C15_1
- GSM8380702 C15_2
- GSM8380703 C15_3
- GSM8380704 C2_1
- GSM8380705 C2_2
- GSM8380706 C2_3
- GSM8380707 C6_1
- GSM8380708 C6_2
- GSM8380709 C6_3
- GSM8380710 WT_Ly5.2_gd_1
- GSM8380711 WT_Ly5.2_gd_2
- GSM8380712 WT_Ly5.2_gd_3
- GSM8380713 DERL2_1
- GSM8380714 DERL2_2
- GSM8380715 DERL2_3
- GSM8380716 DERL7_1
- GSM8380717 DERL7_2
- GSM8380718 DERL7_3
- GSM8380719 BC35
- GSM8380720 BC36
- GSM8380721 BC37
- GSM8380722 BC5
- GSM8380723 BC8
Similar datasets
- GSE328222 Acute rapamycin treatment reveals novel mechanisms of dysfunction in a maternal inflammation mouse model 32 samples
- GSE260997 Mutant IDH inhibitors induce lineage differentiation in IDH-mutant Oligodendroglioma III 2458 samples
- GSE246221 A Mouse Model for Metabolic Dysfunction-associated Steatotic Liver Disease and Hepatocellular Carcinoma [RNA-seq] 148 samples
- GSE331030 Lentiviral single-cell MPRA of synthetic enhancers reveals motif affinity-based encoding of cell state specificity [sc-lentiMPRA 2] 66 samples
- GSE335842 Single-Cell RNA sequencing reveals clonally-expanded CD4+ tissue-resident memory T cells in Histidyl-tRNA Synthetase-induced myositis 38 samples
- GSE304108 Drug Screening in 3D Microtumors Reveals DDR1/2-MAPK12-GLI1 as a Vulnerability in Cancer-Associated Fibroblasts 29 samples
- GSE158626 Targeting Set7 in an experimental model of diabetic nephropathy 28 samples
- GSE248947 Spatiotemporal control of SMARCA5 by a MAPK-RUNX1 axis distinguishes mutant KRAS-driven pancreatic malignancy from tissue regeneration (RNA-Seq) 28 samples
Share this dataset
Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.