The role of heterogeneous nuclear ribonucleoprotein K in the progression of chronic myeloid leukemia
The role of heterogeneous nuclear ribonucleoprotein K in the progression of chronic myeloid leukemia
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异质核核糖核蛋白K在慢性粒细胞白血病进展中的作用
DOI：
10.1007/s12032-009-9267-z
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发表时间：
2010-09-01
期刊：
影响因子：
3.4
通讯作者：
Liu, Xiaoli
中科院分区：
文献类型：
--
作者：
Du, Qingfeng;Wang, Li;Liu, Xiaoli
慢性粒细胞白血病（CML）是一种造血干细胞肿瘤性疾病。核内不均一核糖核蛋白K（hnRNPK）可上调癌细胞中某些癌基因的转录活性。本研究的目的是验证hnRNPK在CML患者中的表达模式，探讨其与BCR-ABL及一些异常信号通路的关系，并揭示hnRNPK在CML进展中的作用。在这项研究中，15例CML患者（9例慢性期和6例急变期）入组本研究。采用Western blotting和荧光定量实时逆转录聚合酶链反应检测患者外周血单个核细胞（MNCs）中hnRNPK的表达。还测定了用Ras-MAPK（PD 98059）、PI 3 K/AKT（LY 294002）、JAK/STAT（AG 490）信号通路和BCR-ABL [甲磺酸伊马替尼（IM）]抑制剂处理后K562细胞系和伊马替尼耐药白血病细胞系K562 R中的hnRNPK表达水平。结果表明，与正常人相比，CML患者的MNCs中hnRNPK在蛋白质和基因模式上均存在过度表达。CML急变期患者的MNCs中其表达水平明显高于CML慢性期患者（P<0.01）。经PD 98059（4、8、24、48 h）和IM（48 h）处理后，白血病细胞株hnRNPK的表达水平较DMSO对照组明显降低（P<0.05）。结果提示，hnRNPK的过度表达可能促进CML的进展，而hnRNPK的过度表达受BCR-ABL和Ras-MAPK信号通路的调节。hnRNPK可能成为CML演变的标志物和治疗靶点。
Chronic myeloid leukemia (CML) is a neoplastic disease of the hematopoietic stem cell. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) may up-regulate the transcriptional activity of some oncogenes in cancerous cells. The aim of this study was to verify the expression pattern of hnRNPK in patients with CML, to explore its association with BCR-ABL and some abnormal signaling pathways, and to discover how hnRNPK contributes to the progression of CML. In this study, 15 patients with CML (9 in chronic phase and 6 in blast crisis) were enrolled in this study. The expression of hnRNPK in mononuclear cells (MNCs) from these patients was detected by Western blotting and fluorimeter-based quantitative real-time reverse transcriptase polymerase chain reaction. hnRNPK expression levels in K562 cell line and imatinib-resistant leukemic cell line K562R, following the treatments with the inhibitors of Ras-MAPK (PD98059), PI3K/AKT (LY294002), JAK/STAT (AG490) signaling pathways, and BCR-ABL [imatinib mesylate (IM)], were also determined. As the results, the overexpression of hnRNPK in protein and gene patterns was detected in MNCs from patients with CML comparing with normal donors. Especially, its level in MNCs from patients with CML-blast crisis was significantly higher than in CML-chronic phase cells (P<0.01). After the treatment with PD98059 (at 4, 8, 24, and 48 h) and IM (at 48 h), the expression levels of hnRNPK in leukemic cell lines were decreased, comparing with DMSO control group (P<0.05). In conclusion, the results suggest that the overexpression of hnRNPK, which is regulated by BCR-ABL and Ras-MAPK signaling pathways, may promote the progression of CML. hnRNPK would be a potential marker and therapeutic target of CML evolution.