The ratio of SRSF1-IS1/IS2 mRNA is a marker of clinical prognosis in pediatric B-ALL and SRSF1 isoforms differentially regulate apoptosis and proliferation on leukemic cells

Abstract

Abstract Background Serine/Arginine Splicing Factor 1 (SRSF1) is a prototypical splicing factor, which plays an important role in constitutive splicing and alternative splicing (AS). SRSF1 can be highly expressed and act as a key oncogene in several malignant solid tumors. SRSF1 is expressed as two isoforms, including isoform 1 (full-length) and isoform 2 (short), the latter lacking the C-terminal RS domain. The role of both isoforms in pediatric acute lymphoblastic leukemia (ALL) is not completely understood. Methods In this study, we detected the mRNA expression of SRSF1 isoform 1 and isoform 2 in bone marrow samples from newly diagnosed (ND) pediatric B cell acute lymphoblastic leukemia (B-ALL) patients and non-hematologic malignancy (immune thrombocytopenia patients, ITP) by qRT-PCR. Functional analysis of SRSF1 isoform 1 and isoform 2 in Nalm-6 cell was conducted in vitro. ResultsHigher mRNA level of isoform 1 was associated with shortened 5-year EFS and OS. Lower mRNA level of isoform 2 was associated with shortened 5-year EFS. Simultaneously we first identified the ratio of isoform 1/isoform 2 (IS1/IS2) was negatively associated with 5-year overall survival (OS) and 5-year event-free survival (EFS). Further, we found that human leukemia cell lines showed significantly higher levels of SRSF1 isoform 1 protein and lower levels of SRSF1 isoform 2 protein comparing with normal B cells. SRSF1 isoform 1 can promote leukemia cell proliferation and inhibit apoptosis, but not by SRSF1 isoform 2 in vitro. Conclusions Our observations demonstrate distinct roles for SRSF1 isoforms in pediatric B-ALL. The ratio of SRSF1-IS1/IS2 mRNA maybe as a marker of clinical prognosis in pediatric B-ALL.