DNMT3A low-expression is correlated to poor prognosis in childhood B-ALL and confers resistance to daunorubicin on leukemic cells
Weijing Li,
Shuguang Liu,
Chanjuan Wang,
Lei Cui,
Xiaoxi Zhao,
Wei Liu,
Ruidong Zhang,
Zhigang Li
Affiliations
Weijing Li
Laboratory of Hematologic Diseases, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health
Shuguang Liu
Laboratory of Hematologic Diseases, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health
Chanjuan Wang
Beijing Key Laboratory of Pediatric Hematology-Oncology
Lei Cui
Laboratory of Hematologic Diseases, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health
Xiaoxi Zhao
Laboratory of Hematologic Diseases, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health
Wei Liu
Department of Hematology Oncology, Children’s Hospital Affiliated to Zhengzhou University
Ruidong Zhang
Beijing Key Laboratory of Pediatric Hematology-Oncology
Zhigang Li
Laboratory of Hematologic Diseases, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health
Abstract Background Little is known about DNMT3A expression and its prognostic significance in childhood B cell acute lymphoblastic leukemia (B-ALL). Methods We determined DNMT3A mRNA expression in 102 children with B-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 Reh and 697 B-ALL cell lines. Cell proliferation activity after treated with daunorubicin (DNR) was determined by CCK8 assay in DNMT3A KO Reh and 697 cell lines. Results DNMT3A expression in B-ALL patients who were in continuous complete remission (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 B-ALL. Knock-out of DNMT3A in Reh and 697 cell lines significantly increased IC50 of DNR (P = 0.0201 and 0.0022 respectively), indicating elevated resistance to DNR. Conclusion Low expression of DNMT3A associates with poor prognosis in children with B-ALL. Knock-out of DNMT3A confers resistance to DNR on leukemic cells.
