DNMT3A Low-Expression is Correlated to Poor Prognosis in Childhood B Cell Precursor Acute Lymphoblastic Leukemia and Confers Resistance to Daunorubicin on Leukemic Cells

Abstract

\n Background Little is known about DNMT3A expression and its prognostic significance in childhood B cell precursor acute lymphoblastic leukemia (BCP-ALL). MethodsWe determined DNMT3A mRNA expression in 102 children with BCP-ALL. Correlations with relapse-free survival (RFS) and common clinical characteristics were analyzed. DNMT3A was stably knocked out by CRISPR/Cas9 gene editing technology in 697 cell line. Cell proliferation activity after treated with daunorubicin was determined by CCK8 assay in DNMT3A KO 697 cell line.Results DNMT3A expression in BCP-ALL patients who were in CCR was higher than in those who got relapse (P=0.0111). Receiver operating characteristic curve showed prognostic significance of DNMT3A expression (P=0.003). Low expression of DNMT3A (<0.197) was significantly correlated with poor RFS (P<0.001) in children with BCP-ALL. Knock-out of DNMT3A in 697 cell line significantly increased IC50 of daunorubicin (P=0.0057), indicating elevated resistance to daunorubicin. ConclusionsLow expression of DNMT3A associates with poor prognosis in children with BCP-ALL. Knock-out of DNMT3A confers resistance to daunorubicin on leukemic cells.