1. Correlation of SRSF1 and PRMT1 expression with clinical status of pediatric acute lymphoblastic leukemia
- Author
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Mei Mei, Xiaoxi Zhao, Shanshan Zhu, Huyong Zheng, Zhigang Li, Xiao Liu, Limin Zou, Wei Zhang, Chao Gao, Han Zhang, Shilai Bao, and Chaohao Du
- Subjects
Male ,Vincristine ,medicine.medical_specialty ,Cancer Research ,Protein-Arginine N-Methyltransferases ,Microarray ,Adolescent ,medicine.medical_treatment ,Biology ,Acute lymphoblastic leukemia ,lcsh:RC254-282 ,Pathogenesis ,Arginine methylation ,Internal medicine ,medicine ,Humans ,Child ,Molecular Biology ,Regulation of gene expression ,Chemotherapy ,Hematology ,Serine-Arginine Splicing Factors ,lcsh:RC633-647.5 ,Research ,Infant ,Nuclear Proteins ,RNA-Binding Proteins ,lcsh:Diseases of the blood and blood-forming organs ,Protein arginine methyltransferase 1 (PRMT1) ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Splicing factor SRSF1 ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Repressor Proteins ,Leukemia ,medicine.anatomical_structure ,Cell Transformation, Neoplastic ,Oncology ,Child, Preschool ,Cancer research ,Female ,Bone marrow ,medicine.drug ,Alternative splicing - Abstract
Background Acute 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, SFRS1 was found to be up-regulated. Serine/arginine-rich splicing factor 1 (SRSF1, also termed SF2/ASF), encoded by the SFRS1 gene, 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. Methods Matched, 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. Results We 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. Conclusions Our results indicate that SRSF1 serves as an anti-apoptotic factor and potentially contributes to leukemogenesis in pediatric ALL patients by cooperating with PRMT1.
- Published
- 2012