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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 24, 2020 |
| Title |
STAT5BN642H is a driver mutation for T-cell neoplasia (RNA-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| 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.
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| Overall design |
Total RNA extracted from wt and hSTAT5B and hSTAT5BN642H (transgenic) CD8+ T-cells (5 biological replicates/sample of WT and hSTAT5BN642H mice, 4 biological repicates/sample of hSTAT5B mice), RNA-seq 50 bp single-end libraries sequenced on HiSeq 2500 (Illumina), to compare gene expression profiles
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| Contributor(s) |
Pham HT, Grausenburger R, Moriggl R |
| Citation(s) |
31123029 |
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| Submission date |
Jan 19, 2017 |
| Last update date |
Feb 24, 2020 |
| Contact name |
Ha T T Pham |
| E-mail(s) |
ha.pham@lbicr.lbg.ac.at
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| Organization name |
Ludwig Boltzmann Institute for Cancer Research
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| Lab |
Richard Moriggl
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| Street address |
SCHWARZSPANIERSTR 17
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| City |
Wien |
| ZIP/Postal code |
A1090 |
| Country |
Austria |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (14)
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| GSM2463814 |
wild-type, replicate 4 |
| GSM2463816 |
wild-type, replicate 5 |
| GSM2463818 |
hSTAT5B, replicate 1 |
| GSM2463820 |
hSTAT5B, replicate 2 |
| GSM2463822 |
hSTAT5B, replicate 3 |
| GSM2463824 |
hSTAT5B, replicate 4 |
| GSM2463826 |
STAT5BN642H, replicate 1 |
| GSM2463828 |
STAT5BN642H, replicate 2 |
| GSM2463830 |
STAT5BN642H, replicate 3 |
| GSM2463832 |
STAT5BN642H, replicate 4 |
| GSM2463834 |
STAT5BN642H, replicate 5 |
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| This SubSeries is part of SuperSeries: |
| GSE104577 |
STAT5BN642H is a driver mutation for T-cell neoplasia |
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| Relations |
| BioProject |
PRJNA362591 |
| SRA |
SRP097155 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE93847_RAW.tar |
2.4 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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