文章：

抑制MerTK增加T细胞急性淋巴细胞白血病的化疗敏感性并降低致瘤潜能

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

原文发布日期：2013-01-25

DOI: 10.1038/bcj.2012.46

类型: Original Article

开放获取: 是

英文摘要：

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.

摘要翻译： 

儿童白血病存活率在过去几十年显著提高。然而，当前治疗方案对复发白血病病例仍然基本无效，且会导致较高比例的慢性健康问题。因此，我们仍需寻找新的治疗选择。本研究发现，约半数儿童T细胞白血病患者样本及T细胞急性淋巴细胞白血病（T-ALL）细胞系中存在Mer酪氨酸激酶（MerTK）的异常表达。配体Gas6对MerTK的刺激会激活促存活蛋白Erk 1/2和Stat5，其中MerTK依赖的STAT通路激活是白血病研究中的新发现。此外，抑制MerTK表达能增强T-ALL细胞对化疗药物的敏感性，并在甲基纤维素集落形成实验中降低Jurkat T-ALL细胞系的致癌潜力。最后，在白血病异种移植小鼠模型中，抑制MerTK表达能显著延长中位生存期（从30.5天至60天，P<0.0001）。这些结果表明，MerTK抑制是一种前景广阔的白血病治疗策略，或可降低现有化疗药物用量，从而减少治疗相关毒性反应的发生率。

原文链接：

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