Prognostic significance of huntingtin interacting protein 1 expression on patients with acute myeloid leukemia.
Prognostic significance of huntingtin interacting protein 1 expression on patients with acute myeloid leukemia.
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亨廷顿蛋白相互作用蛋白1表达对急性髓系白血病患者的预后意义
DOI：
10.1038/srep45960
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发表时间：
2017-04-28
影响因子：
4.6
通讯作者：
Jin J
中科院分区：
文献类型：
--
作者：
Wang J;Yu M;Guo Q;Ma Q;Hu C;Ma Z;Yin X;Li X;Wang Y;Pan H;Wang D;Huang J;Meng H;Tong H;Qian W;Jin J
亨廷顿蛋白相互作用蛋白1 （HIP1）是一种内吞蛋白，在多种人类癌症中过表达，并参与白血病的致癌易位。然而，hip1表达对AML的预后影响尚不清楚。在这项研究中，通过实时定量PCR对270例AML患者骨髓母细胞中的hip1转录物进行了定量分析。因此，高hip1表达在老年患者、npm1和dnmt3突变的M4/M5形态和基因中更为常见，而在我们的AML患者的有利核型亚群和cebpad双等位基因突变中代表性不足。我们还发现高hip1表达者的血红蛋白水平较低。此外，hip1的过表达与较低的总生存率相关。在独立的TCGA队列患者中验证了hip1表达的预后价值。值得注意的是，在来自两个独立队列的高hip1表达者中，miR-16、miR-15a、miR-28和miR-660均出现上调。在体外实验中，siRNA干扰hip1的表达可抑制白血病细胞的增殖，并且在沉默hip1表达后，THP-1和Kasumi细胞系中这些mirna的表达下调。总之，hip1基因表达可能是AML患者总生存率的可靠预测因子。
Huntingtin interacting protein 1 (HIP1) is an endocytic protein which is overexpressed in a variety of human cancers and involved in cancer-causing translocation in leukemia. However, the prognostic impact ofHIP1expression on AML remains unclear. In this study, quantification ofHIP1transcript by real-time quantitative PCR in bone marrow blasts was performed in 270 AML patients. As a result, highHIP1expression was seen more frequently in older patients, M4/M5 morphology and genes ofNPM1andDNMT3Amutations, and underrepresented in favorable karyotype subgroups andCEBPAdouble allele mutations in our AML patients. We also found highHIP1expressers showed lower levels of hemoglobin. In addition, overexpression ofHIP1was associated with an inferior overall survival. The prognostic value ofHIP1expression was validated in patients from an independent TCGA cohort. Notably, up-regulation of miR-16, miR-15a, miR-28 and miR-660 were seen in highHIP1expressers from the two independent cohorts.In vitro, interfereing ofHIP1expression by siRNA suppressed the proliferation of leukemic cells, and downregulation of these miRNAs were seen in THP-1 and Kasumi cell lines after silencingHIP1expression. In conclusion, theHIP1gene expression might serve as a reliable predictor for overall survival in AML patients.