Journal
BLOOD CANCER JOURNAL
Volume 3, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bcj.2012.46
Keywords
MerTK; receptor tyrosine kinase; T-cell leukemia; xenograft mouse model
Categories
Funding
- NIH [RO1CA137078]
- National Heart, Lung and Blood Institute [F32HL096416]
- NIH/NCRR Colorado CTSI [UL1 RR025780]
- Damon Runyon Cancer Research Foundation [CI-39-07]
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Pediatric leukemia survival rates have improved dramatically over the past decades. However, current treatment protocols are still largely ineffective in cases of relapsed leukemia and are associated with a significant rate of chronic health conditions. Thus, there is a continued need for new therapeutic options. Here, we show that mer receptor tyrosine kinase (MerTK) was abnormally expressed in approximately one half of pediatric T-cell leukemia patient samples and T-cell acute lymphoblastic leukemia (T-ALL) cell lines. Stimulation of MerTK by the ligand Gas6 led to activation of the prosurvival proteins Erk 1/2 and Stat5, and MerTK-dependent activation of the STAT pathway in leukemia represents a novel finding. Furthermore, inhibition of MerTK expression increased the sensitivity of T-ALL cells to treatment with chemotherapeutic agents and decreased the oncogenic potential of the Jurkat T-ALL cell line in a methylcellulose colony-forming assay. Lastly, inhibition of MerTK expression significantly increased median survival in a xenograft mouse model of leukemia (30.5 days vs 60 days, P<0.0001). These results suggest that inhibition of MerTK is a promising therapeutic strategy for the treatment of leukemia and may allow for dose reduction of currently used chemotherapeutics resulting in decreased rates of therapy-associated toxicities. Blood Cancer Journal (2013) 3, e101; doi: 10.1038/bcj.2012.46; published online 25 January 2013
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