A majority of acute promyelocytic leukaemia (APL) cases are characterized by the PML-RAR alpha fusion gene. Previous studies have shown that neutrophil elastase (NE) can cleave PML-RAR alpha and is important for the development of APL. Here, we demonstrate that one of the cleavage products of PML-RAR alpha, NLS-RAR alpha, can block cell differentiation by repressing the expression of the target genes within the retinoic acid signalling pathway. The results of reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis showed that NLS-RAR alpha depressed the expression of the cell differentiation marker protein, CD11b and CEBPb, as well as the retinoic acid signalling pathway target genes, RAR beta and CEBP epsilon. Studies have shown that NLS-RAR alpha forms heterodimers with retinoid X receptor alpha(RXR alpha) and interacts with SMRT. When treated with all-trans retinoic acid (ATRA), NLS-RAR alpha exhibits diminished transcriptional activity compared to RAR alpha. Moreover, in the presence of high doses of ATRA, NLS-RAR alpha could be degraded along with the consequent transactivation of retinoic acid signalling pathway target genes and cell differentiation induction in a dose- and time-dependent manner. Together, these results indicate that NLS-RAR alpha blocks cell differentiation by inhibiting the retinoic acid signalling pathway. (C) 2020 The Authors. Published by Elsevier Inc.