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Elevated mRNA transcripts of non-homologous end-joining genes in pediatric acute lymphoblastic leukemia

Leukemia volume 21, pages 2061–2064 (2007)Cite this article

Human cells are frequently exposed to DNA double-strand breaks (DSB) that are generated either by endogenous (for example, V(D)J recombination and reactive oxygen species) or by exogenous (for example, ionizing radiation and chemotherapy regimens) agents. To repair DSB and maintain genome integrity, human cells have evolved two major repair pathways: non-homologous end-joining (NHEJ) and homologous recombination (HR). HR uses homologous DNA strand as a template to repair DSB and is an error-free process.1 NHEJ repairs DSB by directly re-ligating DNA ends, which may be error-prone and may produce mis-ligation between the two chromosome ends.2, 3, 4 In this regard, it has been shown that NHEJ repair is involved in the generation of certain chromosomal translocations in acute myeloid and lymphoid leukemia.2, 3, 5 These chromosome translocations are thought to be correlated with highly activated NHEJ activity.2, 3 However, the expressions of NHEJ genes in these tumors are poorly understood so far. In this study, we report a survey of NHEJ mRNA expressions in pediatric acute lymphoblastic leukemia (ALL).

In summary, we show here that mRNA expressions of NHEJ genes were upregulated in pediatric ALL. To our knowledge, this study is the first to present the mRNA expression of Cernunnos/XLF, which was newly identified as an NHEJ member in 2006,6, 7 as well as of other NHEJ components including Artemis, XRCC4 and DNA ligase IV in pediatric ALL. We showed that overexpressions of NHEJ genes were closely associated with malignant leukemic cells, since elevations of NHEJ mRNA transcripts were found only in fresh ALL and in relapsed cases, but not in thalassemia, complete remission or peripheral blood of normal individuals. Elevations of NHEJ mRNAs could also be found in malignant cell lines K562 and BJAB, but not in oral cancer. Therefore, we propose that upregulation of NHEJ mRNA transcripts is a characteristic of pediatric ALL. This feature may be valuable for proper prognosis or for providing strategies for treatment of this malignancy.

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Acknowledgements

This work was supported by Kaohsiung Medical University Pediatric Cancer Funds (QP094001 to SSC) and Kaohsiung Medical University Cancer Funds (QC094004 to CSL).

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Authors and Affiliations

  1. Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    S-S Chiou, C-H Hung & T-T Chang

  2. Department of Pediatrics, Faculty of Pediatrics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    S-S Chiou, Y-J Jong & C-H Hung

  3. Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, Tainan, Taiwan

    J-L Huang

  4. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Y-S Tsai, T-F Chen, S-H H Juo, Y-J Jong & C-S Lin

  5. Department of Otolaryngology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    K-W Lee

  6. Department of Otolaryngology, Faculty of Otolaryngology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    K-W Lee

  7. Graduate Institute of Medical Genetics, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    S-H H Juo

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  1. S-S Chiou
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Correspondence to C-S Lin.

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Chiou, SS., Huang, JL., Tsai, YS. et al. Elevated mRNA transcripts of non-homologous end-joining genes in pediatric acute lymphoblastic leukemia. Leukemia 21, 2061–2064 (2007). https://doi.org/10.1038/sj.leu.2404742

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