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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 04, 2022 |
| Title |
The PAX5-JAK2 translocation acts as a dual-hit mutation that promotes aggressive B-cell leukemia via nuclear STAT5 activation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
While PAX5 is an important tumor suppressor in B-ALL, it is also involved in oncogenic translocations coding for PAX5 fusion proteins. PAX5-JAK2 encodes a protein consisting of the PAX5 DNA-binding region fused to the constitutively active JAK2 kinase domain. Here, we studied the oncogenic function of PAX5-JAK2 in a mouse model expressing it from the endogenous Pax5 locus. The Pax5Jak2/+ mice rapidly developed an aggressive B-ALL in the absence of another cooperating mutation. The DNA-binding function and kinase activity of Pax5-Jak2, as well as IL-7 signaling, all contributed to leukemia development. Interestingly, all Pax5Jak2/+ tumors lost the wild-type Pax5 allele, allowing efficient DNA binding of Pax5-Jak2. While we could not find evidence for a nuclear role of Pax5-Jak2 as an epigenetic regulator, active phosphorylated Stat5 was present at a high level in Pax5Jak2/+ B-ALL tumors, consistent with increased expression of Stat5 target genes. Together, these data identified Pax5-Jak2 as an important nuclear driver of leukemia formation by maintaining phosphorylated Stat5 levels in the nucleus.
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| Overall design |
6 Bio-ChIP-Seq samples, 2 experiments, 2 replicates per condition: experiment 1: 29936 + 29938 (wild type) experiment 2: 38870 + 40031 (experimental), 40030 + 40031 (control) 19 ChIP-Seq samples, 5 experiments: experiment 1: 100885-100883, 12 samples experiment 2: 138001 (input), 138002 (experimental), 138003 (control) experiment 3: 35059 + 35061 (wild type) experiment 4: 35327 (input) experiment 5: 8265 (wild type)
21 RNA-Seq samples, 4 experiments, 2-4 replicates each; experiment 1: 36328/36329, 36346-36348 (6 samples); experiment 2: 24394-24397 (4 samples); experiment 3: 38492-38497 (5 samples); experiment 4: 99560-99565 (6 samples)
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| Contributor(s) |
Jurado S, Fedl AS, Jaritz M, Kostanova-Poliakova D, Malin SG, Mullighan CG, Strehl S, Fischer M, Busslinger M |
| Citation(s) |
35156727 |
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| Submission date |
May 20, 2021 |
| Last update date |
Apr 20, 2022 |
| Contact name |
Meinrad Busslinger |
| E-mail(s) |
meinrad.busslinger@imp.ac.at
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| Organization name |
IMP
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| Lab |
Busslinger
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| Street address |
Campus-Vienna-Biocenter 1
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| City |
Vienna |
| ZIP/Postal code |
A-1030 |
| Country |
Austria |
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| Platforms (2) |
| GPL11002 |
Illumina Genome Analyzer IIx (Mus musculus) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (46)
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| Relations |
| BioProject |
PRJNA731504 |
| SRA |
SRP320709 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE174775_RAW.tar |
8.3 Gb |
(http)(custom) |
TAR (of BW, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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