Title: Quantitative profiling of N6-methyladenosine methylome at childhood Ph positive B-cell acute lymphoblastic leukemia reveals a potential mechanism for transcriptional regulation and differential methylation pattern

Abstract:

m6A is the most common methylation modification of mRNA. Recent researches have revealed a critical role of m6A in tumorigenesis. ALL is the most common malignant tumor in children. We profile next-generation sequencing  in the bone marrow of childhood B-ALL at diagnosis. The results showed that the expression levels of FTO, METTL14 and YTHDF2  in ALL patients were significantly up-regulated (P<0.05) compared with control group. We found that m6A is a highly conserved modification of mRNA. The m6A modification sites have a typical consensus sequence RRACU. The m6A modification sites in B-ALL are enriched near the stop codons and within 3’UTR. GO analysis showed that the major molecular functions in these transcripts were responsible for molecule binding, transferase, transcription regulatory, and transferase activity. The cellular components were responsible for intracellular, nucleus and membrane-bounded organelle. The biological processes were responsible for metabolic process. The KEGG indicates that virus infection and type I interferons pathway are crucial. The versatile roles of m6A in childhood B-ALL is significant in mediating mRNA decay.