Expression of the promyelocytic leukemia protein without the nuclear localization signal as a novel diagnostic marker for acute promyelocytic leukemia

  • Authors:
    • Ting Xu
    • Xiao-Qun Yang
    • Kai-Ling Jiang
    • Hui Wang
    • Peng-Peng Ma
    • Liang Zhong
    • Bei-Zhong Liu
  • View Affiliations

  • Published online on: Monday, January 9, 2017
  • Pages:986-994 DOI: 10.3892/or.2017.5357
0

Abstract

Promyelocytic leukemia-retinoic acid receptor α (PML-RARα) is a fusion protein generated by the t(15;17)(q22;q12) translocation associated with acute promyelocytic leukemia (APL). PML-RARα is cleaved by neutrophil elastase, an early myeloid-specific serine protease, leading to translocation of the nuclear localization signal (NLS) of the PML protein to the N-terminal of RARα, and the mutational product PML(NLS-). The present study was designed to analyze the role of the NLS in mediating PML transport into the nucleus and to evaluate the value of measuring NLS translocation in the early diagnosis of APL. PML and PML(NLS-) localization was examined by immunofluorescence (IF). The interaction between PML/PML(NLS-) and importin α was detected by an in vivo binding assay using co-immunoprecipitation and double IF labeling. Twenty-seven untreated APL patients with PML-RARα and 22 non-APL controls were evaluated. PML(NLS-) was detected in primary APL, but not non-APL cells. IF showed that PML was localized to the nucleus, interacted with importin α in vivo, and co-localized in the PML nuclear bodies. PML(NLS-) was primarily localized in the cytoplasm and the interaction with importin α was lost. IF had a sensitivity and specificity of 92.6 and 77.3%, respectively, for diagnosing APL. These data suggest that PML(NLS-) may be a novel diagnostic biomarker for APL.

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February 2017
Volume 37 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

2015 Impact Factor: 2.486
Ranked #31/211 Oncology
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Copy and paste a formatted citation
APA
Xu, T., Yang, X., Jiang, K., Wang, H., Ma, P., Zhong, L., & Liu, B. (2017). Expression of the promyelocytic leukemia protein without the nuclear localization signal as a novel diagnostic marker for acute promyelocytic leukemia. Oncology Reports, 37, 986-994. http://dx.doi.org/10.3892/or.2017.5357
MLA
Xu, T., Yang, X., Jiang, K., Wang, H., Ma, P., Zhong, L., Liu, B."Expression of the promyelocytic leukemia protein without the nuclear localization signal as a novel diagnostic marker for acute promyelocytic leukemia". Oncology Reports 37.2 (2017): 986-994.
Chicago
Xu, T., Yang, X., Jiang, K., Wang, H., Ma, P., Zhong, L., Liu, B."Expression of the promyelocytic leukemia protein without the nuclear localization signal as a novel diagnostic marker for acute promyelocytic leukemia". Oncology Reports 37, no. 2 (2017): 986-994. http://dx.doi.org/10.3892/or.2017.5357