title: RNA-Seq profiling reveals aberrant RNA splicing in patient with adult acute myeloid leukemia during treatment.
abstract: BACKGROUND
  Multiple genetic alterations that affect the process of acute myeloid leukemia (AML) have been discovered, and more evidence also indicates that aberrant splicing plays an important role in cancer.
  
  
  METHODS
  We present a RNA-Seq profiling of an AML patient with complete remission after treatment, to analyze the aberrant splicing of genes during treatment. We sequenced 3.97 and 3.32 Gbp clean data of the AML and remission sample, respectively. Firstly, by analyzing biomarkers associated with AML, to assist normal clinical tests, we confirmed that the patient was anormal karyo type, with NPM1 and IDH2 mutations and deregulation patterns of related genes, such as BAALC, ERG, MN1 and HOX family. Then, we performed alternative splicing detection of the AML and remission sample.
  
  
  RESULTS
  We detected 91 differentially splicing events in 68 differentially splicing genes (DSGs) by mixture of isoforms (MISO). Considering Psi values (Ψ) and confidence intervals, 25 differentially expressed isoforms were identified as more confident isoforms, which were associated with RNA processing, cellular macromolecule catabolic process and DNA binding according to GO enrichment analysis. An exon2-skipping event in oncogene FOS (FBJ murine osteosarcoma viral oncogene homolog) were detected and validated in this study. FOS has a critical function in regulating cell proliferation, differentiation and transformation. The exon2-skipping isoform of FOS was increased significantly after treatment.
  
  
  CONCLUSIONS
  All the data and information of RNA-Seq provides highly accurate and comprehensive supplements to conventional clinical tests of AML. Moreover, the splicing aberrations would be another source for biomarker and even therapeutic target discovery. More information of splicing may also assist the better understanding of leukemogenesis.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China. 13572101611@163.com.
authors.forename: X-y
authors.initials: XY
authors.lastname: Li
authors.forename: X
authors.initials: X
authors.lastname: Yao
authors.forename: S-n
authors.initials: SN
authors.lastname: Li
authors.forename: A-l
authors.initials: AL
authors.lastname: Suo
authors.forename: Z-p
authors.initials: ZP
authors.lastname: Ruan
authors.forename: X
authors.initials: X
authors.lastname: Liang
authors.forename: Y
authors.initials: Y
authors.lastname: Kong
authors.forename: W-g
authors.initials: WG
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Yao
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D005091:Exons; D020869:Gene Expression Profiling / Q000379:methods*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D000090243:Nucleophosmin; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012326:RNA Splicing; D012074:Remission Induction; D017423:Sequence Analysis, RNA; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C000716967:NPM1 protein, human; D016760:Proto-Oncogene Proteins c-fos; D000090243:Nucleophosmin