Format

Send to

Choose Destination
Cancer Cell. 2013 Jul 8;24(1):90-104. doi: 10.1016/j.ccr.2013.05.006.

Targeting IRAK1 as a therapeutic approach for myelodysplastic syndrome.

Author information

1
Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

Abstract

Myelodysplastic syndromes (MDSs) arise from a defective hematopoietic stem/progenitor cell. Consequently, there is an urgent need to develop targeted therapies capable of eliminating the MDS-initiating clones. We identified that IRAK1, an immune-modulating kinase, is overexpressed and hyperactivated in MDSs. MDS 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 detrimental to MDS cells, while sparing normal CD34(+) cells. Based on an integrative gene expression analysis, we combined IRAK1 and BCL2 inhibitors and found that cotreatment more effectively eliminated MDS clones. In summary, these findings implicate IRAK1 as a drugable target in MDSs.

PMID:
23845443
PMCID:
PMC3711103
DOI:
10.1016/j.ccr.2013.05.006
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center