Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, PR China.
Oncol Rep. 2013 Apr;29(4):1459-66. doi: 10.3892/or.2013.2274. Epub 2013 Feb 5.
Heat shock protein 27 (Hsp27), a member of the heat shock protein (Hsp) family, is critical in the regulation of cancer development, progression and chemotherapy resistance. However, the role of Hsp27 in the pathogenesis of pediatric acute leukemia (AL) remains unknown. In this study, we evaluated the expression levels of Hsp27 in bone marrow samples from 94 children with newly diagnosed acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and 5 leukemia cell lines. Additionally, we transfected a target-specific siRNA duplex against Hsp27 into leukemia cells, and examined the chemosensitivity and cell apoptosis in the response to antitumor drugs. Hsp27 was abundantly expressed in newly diagnosed AML-M4/M5 bone marrow mononuclear cells (BMMCs) and THP-1, OCI/AML-3 leukemia cell lines. Furthermore, its expression was positively correlated with the clinical status in pediatric M4/M5 subtypes. Knockdown of Hsp27 expression increased the chemosensitivity of leukemia cells and the anticancer drug-induced apoptosis. These results support the theory that Hsp27 plays a contributory role in the pathogenesis of pediatric AML-M4/M5. Therefore, Hsp27 may be exploited as a new target for enhancing the efficacy of chemotherapeutic drugs against leukemia.
热休克蛋白 27（Hsp27）是热休克蛋白（Hsp）家族的一员，在癌症的发生、发展和化疗耐药性的调节中起着关键作用。然而，Hsp27 在儿科急性白血病（AL）发病机制中的作用尚不清楚。在这项研究中，我们评估了 94 例新诊断的急性淋巴细胞白血病（ALL）、急性髓系白血病（AML）和 5 个白血病细胞系的骨髓样本中 Hsp27 的表达水平。此外，我们将针对 Hsp27 的靶向特异性 siRNA 双链体转染到白血病细胞中，并检测了抗肿瘤药物治疗后的化疗敏感性和细胞凋亡。Hsp27 在新诊断的 AML-M4/M5 骨髓单个核细胞（BMMCs）和 THP-1、OCI/AML-3 白血病细胞系中大量表达。此外，其表达与儿科 M4/M5 亚型的临床状态呈正相关。Hsp27 表达的敲低增加了白血病细胞的化疗敏感性和抗癌药物诱导的细胞凋亡。这些结果支持 Hsp27 在儿科 AML-M4/M5 发病机制中起作用的理论。因此，Hsp27 可能被用作增强化疗药物对白血病疗效的新靶点。
