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| Status |
Public on Apr 25, 2013 |
| Title |
Targeting IRAK1 as a therapeutic approach for Myelodysplastic Syndrome |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Myelodysplastic Syndromes (MDS) result from expansion of defective hematopoietic stem/progenitor clones. There is an urgent need to develop targeted therapies capable of eliminating the defective MDS clones. We identified that IRAK1, an immune modulating kinase, is overexpressed and hyperactivated in MDS. MDS-propagating clones treated with a small-molecule IRAK1 inhibitor (IRAK1/4-Inh) exhibited impaired expansion and increased apoptosis, which coincided with TRAF6/NF-κB inhibition. Suppression of IRAK1, either by RNAi or with IRAK1/4-Inh, is selectively detrimental to MDS clones as normal CD34+ cells are preserved. Based on conclusions derived from an integrative gene expression analysis, we combined IRAK1 and BCL2 inhibitors and found that co-treatment collaboratively and selectively eliminated MDS clones. In summary, these findings implicate IRAK1 as a drugable target in MDS.
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| Overall design |
MDSL cells were transduced with lentivirus encoding shRNA targeting human IRAK1 and a negative control (pLKO) for 2.5 days. GFP positive cells were sorted for RNA extraction, labeling, and hybridization. A total of four samples were included, and two groups are assigned. Two replicates are for each group. Comparison comprises mRNA expression profile of TRAF6 knockdown (shT6) v.s. control vector (pLKO). Additionally, MDSL cells were treated with either DMSO or IRAK inhibitor for 24hrs. Cells were subjected to RNA extraction, labeling, and hybridization. A total of four samples were included, and two groups are assigned.
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| Contributor(s) |
Rhyasen GW, Bolanos L, Fang J, Jerez A, Wunderlich M, Rigolino C, Matthews L, Ferrer M, Southall N, Guha R, Keller J, Thomas C, Beverly LJ, Cortelezzi A, Olivia EN, Cuzzola M, Maciejewski JP, Mulloy JC, Starczynowski DT |
| Citation(s) |
23845443 |
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| Submission date |
Apr 24, 2013 |
| Last update date |
Aug 23, 2019 |
| Contact name |
Garrett Rhyasen |
| E-mail(s) |
grhyasen@gmail.com
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| Phone |
5138035317
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| Organization name |
CCHMC
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| Street address |
3333 Burnet Ave
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| City |
Cincinnati |
| State/province |
OHIO |
| ZIP/Postal code |
45229 |
| Country |
USA |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA198793 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE46346_RAW.tar |
34.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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