Effect of microRNA-210 on prognosis and response to chemotherapeutic drugs in pediatric acute lymphoblastic leukemia

Authors

  • Yanyan Mei,

    1. Key Laboratory of Major Diseases in Children (Capital Medical University), Ministry of Education, National Key Discipline of Pediatrics, Ministry of Education, Hematology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China
    Current affiliation:
    1. Department of Pediatrics, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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    • These authors contributed equally to this work.
  • Chao Gao,

    1. Key Laboratory of Major Diseases in Children (Capital Medical University), Ministry of Education, National Key Discipline of Pediatrics, Ministry of Education, Hematology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China
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    • These authors contributed equally to this work.
  • Kailing Wang,

    1. Key Laboratory of Major Diseases in Children (Capital Medical University), Ministry of Education, National Key Discipline of Pediatrics, Ministry of Education, Hematology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China
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  • Lei Cui,

    1. Key Laboratory of Major Diseases in Children (Capital Medical University), Ministry of Education, National Key Discipline of Pediatrics, Ministry of Education, Hematology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China
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  • Weijing Li,

    1. Key Laboratory of Major Diseases in Children (Capital Medical University), Ministry of Education, National Key Discipline of Pediatrics, Ministry of Education, Hematology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China
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  • Xiaoxi Zhao,

    1. Key Laboratory of Major Diseases in Children (Capital Medical University), Ministry of Education, National Key Discipline of Pediatrics, Ministry of Education, Hematology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China
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  • Feifei Liu,

    1. Key Laboratory of Major Diseases in Children (Capital Medical University), Ministry of Education, National Key Discipline of Pediatrics, Ministry of Education, Hematology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China
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  • Minyuan Wu,

    1. Key Laboratory of Major Diseases in Children (Capital Medical University), Ministry of Education, National Key Discipline of Pediatrics, Ministry of Education, Hematology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China
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  • Guoren Deng,

    1. Department of Urology, School of Medicine, University of California, San Francisco, CA, USA
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  • Wei Ding,

    1. Department of Medical Genetics, Capital Medical University, Beijing, China
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  • Hongti Jia,

    1. Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, China
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  • Zhigang Li

    Corresponding author
    1. Key Laboratory of Major Diseases in Children (Capital Medical University), Ministry of Education, National Key Discipline of Pediatrics, Ministry of Education, Hematology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China
    • Correspondence

      Zhigang Li, Key Laboratory of Major Diseases in Children (Capital Medical University), Ministry of Education; National Key Discipline of Pediatrics, Ministry of Education; Hematology Center, Beijing Children's Hospital, Capital Medical University, 56 Nanlishi Road, Beijing 100045, China.

      Tel: 13370115085; Fax: +86 10 59616645;

      E-mail: ericlzg70@hotmail.com

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  • Clinical trial registration number: NCT00707083 (Chi Kong Li, Prince of Wales Hospital, Shatin, Hong Kong) Name of the trial registry: Two combination chemotherapy regimens in treating children with newly diagnosed acute lymphoblastic leukemia.
  • Funding information

    National Natural Science Foundation of China (81170504 and 81200392). Beijing Health Qualified Personnel Program (2011-3-049). National Science & Technology Major Project (2011ZX09302-007-01). National Key Technologies Research & Development Program (2007BAI04B03).

Abstract

Many studies have demonstrated that microRNA-210 (miR-210) expression is intensively upregulated in hypoxic states and differentially regulated in most types of cancer cells. However, the clinical significance of miR-210 and its effects on the response of leukemic cells to chemotherapeutic drugs in childhood acute lymphoblastic leukemia (ALL) remain unknown. In the current study, using real-time qRT-PCR to detect miR-210 expression in bone marrow samples from 114 children at initial diagnosis of ALL, we investigated the prognostic significance of miR-210 and determined its associations with common clinical characteristics and treatment outcome. We further examined its effect on the response to chemotherapeutic drugs in the Reh and RS4;11 cell lines. Results showed that miR-210 expression was significantly lower in patients suffering from relapse and induction failure than in other patients (P < 0.001). Using the receiver operating characteristic curve, 3.8243 was selected as the cut-off value of miR-210 expression in our test cohort (38 cases). A significantly poorer treatment outcome (P < 0.05) was found in the low-expression group and verified in the validation cohort (76 cases, P < 0.05). Patients with low expression of miR-210 and positive minimal residual disease at the end of induction had a much higher rate of relapse or induction failure (= 0.001). Increasing/decreasing miR-210 expression using agomir/antagomir could enhance or reduce the response of Reh cells and RS4;11 cells to daunorubicin/dexamethasone/L-asparaginase and daunorubicin/dexamethasone/vincristine, respectively. In conclusion, miR-210 may be a good prognostic factor and a useful predictor of drug sensitivity, and is a potential therapeutic target for pediatric ALL.

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