PML(NLS¯) protein: A novel marker for the early diagnosis of acute promyelocytic leukemia.

Promyelocyte leukemia-retinoic acid receptor alpha (PML-RAR alpha) is known as a fusion gene of acute promyelocytic leukemia (APL). Previous studies have reported that neutrophil elastase (NE) cleaves PML-RAR alpha in early myeloid cells, which leads to the removal of the nuclear localization signal (NLS) in PML and increases the incidence of APL. The resultant PML without the NLS is termed PML(NLS-). The aim of the present study was to verify the existence and location of the PML(NLS-) protein in NB4 cells. NB4 cells underwent electroporation with the pCMV-HA-NE plasmid to form NB4-HA-NE cells, which were then transplanted to produce tumors in nude mice and samples were collected from patients with APL. Western blot analysis, an immunofluorescence assay, confocal laser microscopy and immunohistochemistry were performed to detect the expression and localization of the PML(NLS-) protein. The findings demonstrated that PML(NLS-) was detectable in the cytoplasm of NB4-HA-NE cells, the tumors in nude mice and in neutrophils from patients with APL. This indicated that PML(NLS-) may be an effective and novel target for the diagnosis of APL.