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Diagnostic value of the dual-luciferase report assay for predicting response to glucocorticoid in children with acute lymphoblastic leukemia

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Abstract

Objective

Resistance to glucocorticoid (GC) is a significant clinical problem in some cases of acute lymphoblastic leukemia (ALL). Current methods of assessing GC resistance are time consuming and have limited reproducibility; in this study, we sought to define a new method of evaluating GC sensitivity and resistance in vitro.

Methods

Based on the mechanisms of GC resistance, we hypothesized that the dual-luciferase report (DLR) assay could reflect the transcription effects of GC downstream of the GC-glucocorticoid receptor signaling pathway, thereby allowing the evaluation of reactions to GC. Sixty-two patients with differential GC response were included in this study. The prednisone induction test was used to divide the children with ALL into two groups: GC sensitive (GCS) and GC resistant (GCR). DLR assay was later conducted on those patients to evaluate its value for diagnosis of the GC reactivity. Receiver operating characteristic curves were used to identify the optimal assay cutoff for identifying response to GC.

Results

Using the DLR assay analysis, we found that GCR subjects showed significantly lower reporter/control ratios for luciferase, as compared with GCS subjects. The optimal cutoff value for GC response was 0.67, with sensitivity of 77.1% and specificity of 93.3%. The DLR assay results were consistent with prednisone induction test results. Further, the DLR assay was simpler, more sensitive, and less time-consuming than the prednisone induction test.

Conclusions

Our study showed that the DLR assay is relatively fast, simple, and sensitive. Accordingly, it could be useful for detecting GC response in children with ALL.

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Author information

Author notes

  1. X. Wang and P. Chen contributed equally to the study.

Authors and Affiliations

  1. Department of Laboratory Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China

    X. Wang & M. Mao

  2. Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

    P. Chen, Y. Sun, Y. Chen, T. Jiang & J. Ouyang

Authors
  1. X. Wang
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  2. P. Chen
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  3. Y. Sun
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  4. Y. Chen
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  5. M. Mao
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  6. T. Jiang
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  7. J. Ouyang
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Corresponding authors

Correspondence to T. Jiang or J. Ouyang.

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Funding

This study was funded by a Grant (No. 81101316) awarded by the Natural Science Foundation of China to Juan Ouyang.

Conflict of interest

All the authors report no conflict of interest concerning the patients or methods used in this study or the findings specified in this paper.

Informed consent

Written informed consents were obtained from all cases.

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Wang, X., Chen, P., Sun, Y. et al. Diagnostic value of the dual-luciferase report assay for predicting response to glucocorticoid in children with acute lymphoblastic leukemia. Clin Transl Oncol 19, 1241–1246 (2017). https://doi.org/10.1007/s12094-017-1661-y

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  • DOI: https://doi.org/10.1007/s12094-017-1661-y

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