|
| Status |
Public on Jan 26, 2016 |
| Title |
Gene expression profiling of KU812 CD25 shRNA vs KU812 control random shRNA |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
In chronic myeloid leukemia (CML) neoplastic stem cells (NCS) represent a critical target of therapy. However, little is known about markers and targets expressed in CML NSC. We examined the phenotype and function of CD34+/CD38─/Lin─ CML LSC by a multi-parameter screen approach employing antibody-phenotyping, mRNA expression profiling, and functional studies, followed by marker-validation using diverse control-cohorts and follow-up samples of CML patients treated with imatinib.
We here show that in contrast to normal stem cells, CD34+/CD38− CML NSC express IL2RA (CD25), and that STAT5 induces expression of CD25 in Lin−/Sca-1+/Kit+ NSC (LSK) in C57/Bl6 mice. Correspondingly, expression of CD25 decreased in the human BCR/ABL1+ stem cell line KU812 upon shRNA-induced STAT5-depletion. The BCR/ABL1-inhibitors nilotinib and ponatinib were also found to decrease STAT5 activity and CD25-expression in KU812 cells and primary CML NSC. A CD25-targeting shRNA augmented the proliferation of KU812 cells in vitro and in vivo in NOD/SCID-IL2R-/- mice. In consecutive experiments the PI3K/mTOR-blocker BEZ235 was found to promote STAT5- and CD25 expression and to produce synergistic anti-neoplastic effects with nilotinib and ponatinib in CML cells. Together, CD25 is a novel STAT5-dependent marker and target in CML NSC.
|
| |
|
| Overall design |
To define differences in mRNA expression patterns in KU812 cells transduced with a random control shRNA or a shRNA against CD25, gene array analyses were performed.
|
| |
|
| Contributor(s) |
Sadovnik I, Valent P |
| Citation(s) |
26607600 |
| Submission date |
Aug 11, 2014 |
| Last update date |
Mar 15, 2019 |
| Contact name |
Markus Jeitler |
| E-mail(s) |
markus.jeitler@meduniwien.ac.at
|
| Organization name |
Medical University Vienna
|
| Street address |
Lazarettgasse 14
|
| City |
Vienna |
| ZIP/Postal code |
A-1090 |
| Country |
Austria |
| |
|
| Platforms (1) |
| GPL16686 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version] |
|
| Samples (2) |
|
| Relations |
| BioProject |
PRJNA258011 |
