Inhibition of MerTK increases chemosensitivity and decreases oncogenic potential in T-cell acute lymphoblastic leukemia

• Published in: Blood cancer journal (New York) Vol. 3; no. 1; p. e101
• Main Authors: Brandao, L N, Winges, A, Christoph, S, Sather, S, Migdall-Wilson, J, Schlegel, J, McGranahan, A, Gao, D, Liang, X, DeRyckere, D, Graham, D K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2013; Springer Nature B.V; Nature Publishing Group
• Subjects: 631/92/609; 692/699/67/1059/99; 692/699/67/1990/283/2125; Biomedical and Life Sciences; Biomedicine; Cancer Research; Hematology; Oncology; Original; original-article; receptor tyrosine kinase; T-cell leukemia; xenograft mouse model; MerTK
• ISSN: 2044-5385; 2044-5385
• DOI: 10.1038/bcj.2012.46

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.