PMID:23353780

Citation	Brandao, LN, Winges, A, Christoph, S, Sather, S, Migdall-Wilson, J, Schlegel, J, McGranahan, A, Gao, D, Liang, X, Deryckere, D and Graham, DK (2013) Inhibition of MerTK increases chemosensitivity and decreases oncogenic potential in T-cell acute lymphoblastic leukemia. Blood Cancer J 3:e101
Abstract	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.
Links	PubMed PMC3556576 Online version:10.1038/bcj.2012.46
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:MERTK		GO:2000107: negative regulation of leukocyte apoptotic process	ECO:0000315:		P		It is shown in figure 3 that a knockout mutation in MerTK leads to increased apoptosis rates in response to chemotherapeutic agents.	complete CACAO 6357
HUMAN:MERTK		GO:0071866: negative regulation of apoptotic process in bone marrow	ECO:0000315:		P		It is shown in figure 3 that a knockout mutation in MerTK leads to increased apoptosis rates in response to chemotherapeutic agents.	complete CACAO 6358
HUMAN:MERTK	involved_in	GO:2000107: negative regulation of leukocyte apoptotic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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