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Series GSE104557 Query DataSets for GSE104557
Status Public on Jan 14, 2023
Title STAT5BN642H is a driver mutation for T-cell neoplasia (RRBS)
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Summary The most frequent mutation in STAT5B is the Asp642His (N642H) mutation that was found in >90 leukemic/lymphoma patients. The development of novel treatment against STAT5BN642H has been hindered by the unavailability of a suitable model and the lack of the direct causal effect of STAT5BN642H on T-cell neoplasia development. We herein demonstrate that mice expressing human STAT5BN642H in the hematopoietic compartment rapidly develop leukemia/lymphoma. The disease is fully transplantable and characterized by the expansion of CD8+ T-cells. hSTAT5BN642H displays persistent and enhanced tyrosine phosphorylation upon cytokine stimulation. This leads to drastic changes in the gene expression profile accompanied by specific alterations in DNA methylation patterns that result in the acceleration of cell cycle progression. hSTAT5BN642H transcriptional activities in T-cell can be inhibited by inhibition of upstream kinases or transcriptional coregulaters, including JAKs, HDACs and BET Bromodomain containing protein. In particular, treatment with ruxolitinib, a JAK kinase inhibitor dramatically reduced tyrosine phosphorylation of hSTAT5BN642H resulting in decreased organ infiltration in vivo. We conclude that hSTAT5BN642H is sufficient to cause leukemia in vivo and JAK inhibitors are potential therapy for leukemic patients with the hSTAT5BN642H.
Overall design DNA methylation profiling by RRBS of CD8+ T cells from 2 wild-type (WT), 2 transgenic hSTAT5B, and 2x transgenic hSTAT5N642H mutant mice, RRBS with 50 bp single-end libraries sequenced on HiSeq 3000/4000 (Illumina)
Contributor(s) Pham HT, Maurer B, Halbritter F, Farlik M, Bock C, Moriggl R
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Submission date Oct 03, 2017
Last update date Jan 16, 2023
Contact name Ha T T Pham
Organization name Ludwig Boltzmann Institute for Cancer Research
Lab Richard Moriggl
City Wien
ZIP/Postal code A1090
Country Austria
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (6)
GSM2803336 hSTAT5B, replicate 1
GSM2803337 hSTAT5B, replicate 2
GSM2803338 hSTAT5BN642H, replicate 1
This SubSeries is part of SuperSeries:
GSE104577 STAT5BN642H is a driver mutation for T-cell neoplasia
BioProject PRJNA413050
SRA SRP119328

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Supplementary file Size Download File type/resource
GSE104557_RAW.tar 134.3 Mb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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