title: Correlation of SRSF1 and PRMT1 expression with clinical status of pediatric acute lymphoblastic leukemia.
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.
authors: Hematology Oncology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Beijing Children's Hospital, Capital Medical University, 56 Nanlishi Road, Beijing 100045, China.
authors: Limin
authors: L
authors: Zou
authors: Han
authors: H
authors: Zhang
authors: Chaohao
authors: C
authors: Du
authors: Xiao
authors: X
authors: Liu
authors: Shanshan
authors: S
authors: Zhu
authors: Wei
authors: W
authors: Zhang
authors: Zhigang
authors: Z
authors: Li
authors: Chao
authors: C
authors: Gao
authors: Xiaoxi
authors: X
authors: Zhao
authors: Mei
authors: M
authors: Mei
authors: Shilai
authors: S
authors: Bao
authors: Huyong
authors: H
authors: Zheng
mesh_terms: D000293:Adolescent; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D008297:Male; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011484:Protein-Arginine N-Methyltransferases / Q000096:biosynthesis* / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D000068103:Serine-Arginine Splicing Factors; D015854:Up-Regulation
chemical_list: D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D000068103:Serine-Arginine Splicing Factors; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases