文章：

CXorf48 是帮助 CML 患者实现无治疗缓解的潜在治疗靶点

CXorf48 is a potential therapeutic target for achieving treatment-free remission in CML patients

原文发布日期：2017-09-01

DOI: 10.1038/bcj.2017.84

类型: Original Article

开放获取: 是

英文摘要：

Although the introduction of tyrosine kinase inhibitors (TKIs) has improved overall survival of patients with chronic myeloid leukemia (CML), about half of the patients eventually relapse after cessation of TKIs. In contrast, the remainder of the patients maintain molecular remission without TKIs, indicating that the patients’ immune system could control proliferation of TKI-resistant leukemic stem cells (LSCs). However, the precise mechanism of immunity against CML-LSCs is not fully understood. We have identified a novel immune target, CXorf48, expressed in LSCs of CML patients. Cytotoxic T cells (CTLs) induced by the epitope peptide derived from CXorf48 recognized CD34+CD38− cells obtained from the bone marrow of CML patients. We detected CXorf48-specific CTLs in the peripheral blood mononuclear cells from CML patients who have discontinued imatinib after maintaining complete molecular remission for more than 2 years. Significantly, the relapse rate of CXorf48-specific CTL-negative patients was 63.6%, compared to 0% in CXorf48-specific CTL-positive patients. These results indicate that CXorf48 could be a promising therapeutic target of LSCs for immunotherapy to obtain durable treatment-free remission in CML patients.

摘要翻译： 

尽管酪氨酸激酶抑制剂（TKI）的引入改善了慢性髓系白血病（CML）患者的总体生存率，但约半数患者在停用TKI后最终会复发。相反，其余患者可在不使用TKI的情况下维持分子学缓解，这表明患者的免疫系统能够控制TKI耐药性白血病干细胞（LSC）的增殖。然而，针对CML-LSCs免疫应答的具体机制尚未完全阐明。我们鉴定出一种新型免疫靶点CXorf48，该蛋白在CML患者的LSCs中表达。由CXorf48来源的表位肽诱导的细胞毒性T细胞（CTL）可识别从CML患者骨髓中获取的CD34+CD38−细胞。在维持完全分子学缓解超过两年后停用伊马替尼的CML患者的外周血单核细胞中，我们检测到了CXorf48特异性CTL。重要的是，CXorf48特异性CTL阴性患者的复发率为63.6%，而阳性患者的复发率为0%。这些结果表明，CXorf48有望成为LSCs的治疗靶点，通过免疫疗法使CML患者获得持久的无治疗缓解。

原文链接：

CXorf48 is a potential therapeutic target for achieving treatment-free remission in CML patients