Correlation of SRSF1 and PRMT1 expression with clinical status of pediatric acute lymphoblastic leukemia.
Correlation of SRSF1 and PRMT1 expression with clinical status of pediatric acute lymphoblastic leukemia.
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SRSF1、PRMT1表达与小儿急性淋巴细胞白血病临床状态的相关性
DOI：
10.1186/1756-8722-5-42
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发表时间：
2012-07-27
影响因子：
28.5
通讯作者：
Zheng H
中科院分区：
文献类型：
--
作者：
Zou L;Zhang H;Du C;Liu X;Zhu S;Zhang W;Li Z;Gao C;Zhao X;Mei M;Bao S;Zheng H
研究背景急性淋巴细胞白血病（acute lymphoblastic leukemia，ALL）是儿童最常见的恶性肿瘤，其发病机制尚不清楚。在使用100名ALL儿童样本的微阵列检测中，发现SFRS 1上调。富含丝氨酸/丝氨酸的剪接因子1（Serine/Stretocine-rich splicing factor 1，SRSF 1），又称SF 2/ASF，是由SFRS 1基因编码的一种原癌蛋白。我们以前的研究表明，SRSF 1可以甲基化的蛋白质精氨酸甲基转移酶1（PRMT 1）在体外，然而，SRSF 1和PRMT 1在儿科ALL的生物学功能是目前unknow.MethodsMatched，新诊断（ND），完全缓解（CR）和复发（RE）的骨髓样本收集57例，以评估SRSF 1和PRMT 1的表达模式。SRSF 1和PRMT 1在白血病发生中的潜在致癌机制也investigated.ResultsWe确定了显着上调SRSF 1和PRMT 1在ND样品。重要的是，SRSF 1和PRMT 1的表达在CR后恢复到正常水平，但在RE样品中反弹。尽管SRSF 1和PRMT 1的表达模式与细胞遗传学亚型无关，但我们对SRSF 1可以预测疾病复发的观察特别令人感兴趣。在前B细胞系中，临床化疗药物阿糖胞苷（Ara-c）或长春新碱（VCR）可以有效地减弱SRSF 1和PRMT 1的表达。此外，SRSF 1和PRMT 1在体内白血病细胞中相互关联。SRSF 1的敲低导致早期细胞凋亡的增加，这可能进一步诱导化疗药物。ConclusionsOur结果表明，SRSF 1作为一种抗凋亡因子，并可能有助于白血病在儿童ALL患者通过与PRMT 1合作。
BackgroundAcute lymphoblastic leukemia (ALL) is the most frequently-occurring malignant neoplasm in children, but the pathogenesis of the disease remains unclear. In a microarray assay using samples from 100 children with ALL,SFRS1was found to be up-regulated. Serine/arginine-rich splicing factor 1 (SRSF1, also termed SF2/ASF), encoded by theSFRS1gene, had been shown to be a pro-oncoprotein. Our previous study indicated that SRSF1 can be methylated by protein arginine methyltransferase 1 (PRMT1) in vitro; however, the biological function of SRSF1 and PRMT1 in pediatric ALL are presently unknown.MethodsMatched, newly diagnosed (ND), complete remission (CR) and relapse (RE) bone marrow samples from 57 patients were collected in order to evaluate the expression patterns of SRSF1 and PRMT1. The potential oncogenic mechanism of SRSF1 and PRMT1 in leukemogenesis was also investigated.ResultsWe identified significant up-regulation of SRSF1 and PRMT1 in the ND samples. Importantly, the expression of SRSF1 and PRMT1 returned to normal levels after CR, but rebounded in the RE samples. Our observation that SRSF1 could predict disease relapse was of particular interest, although the expression patterns of SRSF1 and PRMT1 were independent of the cytogenetic subtypes. In pre-B-cell lines, both SRSF1 and PRMT1 expression could be efficiently attenuated by the clinical chemotherapy agents arabinoside cytosine (Ara-c) or vincristine (VCR). Moreover, SRSF1 and PRMT1 were associated with each other in leukemia cells in vivo. Knock-down of SRSF1 resulted in an increase in early apoptosis, which could be further induced by chemotherapeutics.ConclusionsOur results indicate that SRSF1 serves as an anti-apoptotic factor and potentially contributes to leukemogenesis in pediatric ALL patients by cooperating with PRMT1.
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影响因子：
2.3
作者：
Wang, Lan;Huang, Gang;Zhao, Xinyang;Hatlen, Megan A.;Vu, Ly;Liu, Fan;Nimer, Stephen D.
通讯作者：
Nimer, Stephen D.
影响因子：
8.8
作者：
Mathioudaki, K.;Papadokostopoulou, A.;Scorilas, A.;Xynopoulos, D.;Agnanti, N.;Talieri, M.
通讯作者：
Talieri, M.
影响因子：
4.8
作者：
Goulet, Isabelle;Gauvin, Gabrielle;Cote, Jocelyn
通讯作者：
Cote, Jocelyn
影响因子：
6.1
作者：
Gu, HM;Park, SH;Kim, S
通讯作者：
Kim, S
影响因子：
10.5
作者：
KRAINER, AR;CONWAY, GC;KOZAK, D
通讯作者：
KOZAK, D