title: Expression of the promyelocytic leukemia protein without the nuclear localization signal as a novel diagnostic marker for acute promyelocytic leukemia.
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.
authors.affiliation: Central Laboratory of Yong-Chuan Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.affiliation: Central Laboratory of Yong-Chuan Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Xiao-Qun
authors.initials: XQ
authors.lastname: Yang
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Kai-Ling
authors.initials: KL
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Peng-Peng
authors.initials: PP
authors.lastname: Ma
authors.affiliation: Key Laboratory of Laboratory Medical Diagnostics, Ministry of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Central Laboratory of Yong-Chuan Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Bei-Zhong
authors.initials: BZ
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D015473:Leukemia, Promyelocytic, Acute / Q000175:diagnosis* / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D019913:Nuclear Localization Signals; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D019913:Nuclear Localization Signals; D015514:Oncogene Proteins, Fusion; D000071156:Promyelocytic Leukemia Protein; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; C070576:PML protein, human