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| Status |
Public on Aug 22, 2013 |
| Title |
shRNA Screening Identifies JMJD1C as being required for Leukemia Maintenance |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
We used a mouse model of human AML induced by the MLL-AF9 fusion oncogene, and an epigenetic shRNA library to screen for novel potential drug targets. One of the best candidate drug targets identified in these screens was Jmjd1c. Depletion of Jmjd1c impairs growth and colony formation of mouse MLL-AF9 cells in vitro, as well as establishment of leukemia after transplantation. Depletion of JMJD1C impairs expansion and colony formation of human leukemic cell lines, with the strongest effect observed in the MLL-rearranged ALL cell line, SEM. In both mouse and human leukemic cells, the growth defect upon JMJD1C depletion appears to be primarily due to increased apoptosis, which implicates JMJD1C as a potential therapeutic target in leukemia.
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| Overall design |
To assess the effect of JMJD1C depletion on transcription, we compared the transcriptome of shJMJD1C- and shScr-transduced SEM cells soon after induction of shRNA expression by addition of IPTG to the growth medium. To ensure detecting early changes, 48h was selected as the earliest timepoint displaying JMJD1C depletion and detectable phenotype as monitored by PARP and Caspase 3 cleavage. These observations were consistent across triplicate samples. A total of 138 transcripts were detected as changing between the two conditions (FDR<0.05)
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| Contributor(s) |
Helin K |
| Citation(s) |
24501218 |
| Submission date |
Aug 20, 2013 |
| Last update date |
Mar 15, 2019 |
| Contact name |
Kristian Helin |
| E-mail(s) |
kristian.helin@bric.ku.dk
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| Organization name |
Copenhagen University
|
| Department |
BRIC
|
| Street address |
Ole Maaløes vej 5
|
| City |
Copenhagen |
| ZIP/Postal code |
2200 |
| Country |
Denmark |
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| Platforms (1) |
| GPL16686 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA215939 |
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