文章：

急性髓系白血病（AML）原始细胞中SAMHD1低表达与接受大剂量阿糖胞苷巩固化疗方案后的更好预后相关

Low-level expression of SAMHD1 in acute myeloid leukemia (AML) blasts correlates with improved outcome upon consolidation chemotherapy with high-dose cytarabine-based regimens

原文发布日期：2018-10-19

DOI: 10.1038/s41408-018-0134-z

类型: Article

开放获取: 是

英文摘要：

Sterile alpha motif and histidine/aspartic acid domain containing protein 1 (SAMHD1) limits the efficacy of cytarabine (ara-C) used in AML by hydrolyzing its active metabolite ara-CTP and thus represents a promising therapeutic target. SAMHD1 has also been implicated in DNA damage repair that may impact DNA damage-inducing therapies such as anthracyclines, during induction therapy. To determine whether SAMHD1 limits ara-C efficacy during induction or consolidation therapy, SAMHD1 protein levels were assessed in two patient cohorts of de novo AML from The University of Texas MD Anderson Cancer Center (USA) and the National University Hospital (Singapore), respectively, using immunohistochemistry and tissue microarrays. SAMHD1 was expressed at a variable level by AML blasts but not in a broad range of normal hematopoietic cells in reactive bone marrows. A sizeable patient subset with low SAMHD1 expression (<25% of positive blasts) was identified, which was significantly associated with longer event-free (EFS) and overall (OS) survival in patients receiving high-dose cytarabine (HDAC) during consolidation. Therefore, evaluation of SAMHD1 expression level in AML blasts at diagnosis, may stratify patient groups for future clinical trials combining HDAC with novel SAMHD1 inhibitors as consolidation therapy.

摘要翻译： 

含有无菌α基序和组氨酸/天冬氨酸结构域的蛋白1（SAMHD1）通过水解阿糖胞苷（ara-C）的活性代谢物ara-CTP，限制了该药物在急性髓系白血病（AML）中的疗效，因此成为一个潜在的治疗靶点。SAMHD1还参与DNA损伤修复，这可能影响诱导治疗期间如蒽环类药物等DNA损伤诱导疗法的效果。为确定SAMHD1是否在诱导或巩固治疗期间限制阿糖胞苷疗效，研究分别通过免疫组织化学和组织微阵列技术，对来自美国德克萨斯大学MD安德森癌症中心和新加坡国立大学医院的两个初治AML患者队列进行了SAMHD1蛋白水平评估。AML母细胞中SAMHD1表达水平存在差异，而反应性骨髓中的正常造血细胞表达范围较窄。研究发现相当比例患者（<25%阳性母细胞）呈现低SAMHD1表达，该特征与接受高剂量阿糖胞苷（HDAC）巩固治疗患者更长的无事件生存期（EFS）和总生存期（OS）显著相关。因此，在诊断时评估AML母细胞的SAMHD1表达水平，或可为未来联合HDAC与新型SAMHD1抑制剂作为巩固治疗的临床试验提供患者分层依据。

原文链接：

Low-level expression of SAMHD1 in acute myeloid leukemia (AML) blasts correlates with improved outcome upon consolidation chemotherapy with high-dose cytarabine-based regimens