Liu Jing, Huang Bo, Xiao Yun, Xiong Huo-Mei, Li Jing, Feng Dan-Qin, Chen Xi-Min, Zhang Hai-Bin, Wang Xiao-Zhong
Department of Clinical Laboratory, Second Affiliated Hospital of Nanchang University, Nanchang, China.
Onkologie. 2012;35(6):335-40. doi: 10.1159/000338941. Epub 2012 May 22.
Acute myeloid leukemia (AML) is the most common type of blood cancer in adults. Emerging evidence is establishing a connection between AML and aberrant alternative splicing of pre-mRNA, which may result from aberrant expression of splicing factors, the mediators of splicing reactions.
Using quantitative real-time polymerase chain reaction, we measured mRNA expression of 7 splicing factors belonging to the serine/arginine-rich (SR) protein family, SRSF1 (SF2/ASF), SRSF2 (SC35), SRSF3 (SRp20), SRSF4 (SRp75), SRSF5 (SRp40), SRSF6 (SRp55), and SRSF7 (9G8), and 1 non-SR factor, heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1), in peripheral blood mononuclear cells of 26 patients with newly diagnosed AML and 26 healthy controls. In addition, the relationship between splicing factors and the mRNA splicing patterns of the caspase-8 gene (CASP8) was investigated.
Compared to healthy controls, the expression of splicing factors was obviously aberrant in newly diagnosed AML patients. The expression of SRSF1, SRSF3 and SRSF4 mRNAs was significantly decreased. Moreover, a significant correlation was observed between several splicing factors and caspase-8 pre-mRNA splicing in AML patients, but not in control subjects.
These data suggest that aberrant expression of splicing factors in AML may potentially connect with abnormal expression of oncogenes and be useful for early diagnosis, prognosis, and therapy of AML.
急性髓系白血病（AML）是成人中最常见的血癌类型。新出现的证据正在确立AML与前体mRNA异常可变剪接之间的联系，这可能是由于剪接反应的介导因子——剪接因子的异常表达所致。
我们采用定量实时聚合酶链反应，检测了26例新诊断AML患者和26例健康对照者外周血单个核细胞中7种属于富含丝氨酸/精氨酸（SR）蛋白家族的剪接因子，即SRSF1（SF2/ASF）、SRSF2（SC35）、SRSF3（SRp20）、SRSF4（SRp75）、SRSF5（SRp40）、SRSF6（SRp55）和SRSF7（9G8），以及1种非SR因子——异质性细胞核核糖核蛋白A1（HNRNPA1）的mRNA表达。此外，还研究了剪接因子与半胱天冬酶8基因（CASP8）的mRNA剪接模式之间的关系。
与健康对照相比，新诊断的AML患者中剪接因子的表达明显异常。SRSF1、SRSF3和SRSF4 mRNA的表达显著降低。此外，在AML患者中观察到几种剪接因子与半胱天冬酶8前体mRNA剪接之间存在显著相关性，但在对照受试者中未观察到。
这些数据表明，AML中剪接因子的异常表达可能与癌基因的异常表达相关，并有助于AML的早期诊断、预后评估和治疗。
