Acute promyelocytic leukaemia (APL) with t(11;17)/PLZF‐RARα responds poorly to all‐trans retinoic acid (ATRA) and arsenic trioxide (As₂O₃), in contrast to APL with t(15;17)/PML‐RARα. Molecular studies have shown that histone deacetylase (HDAC) recruited by PLZF‐RARα is associated with the ATRA resistance. Here, we analysed in vitro the differentiation of APL cells with t(11;17) using ATRA, As₂0₃, granulocyte colony‐stimulating factor (G‐CSF), HDAC inhibitor trichostatin A (TSA), or combinations of these. Although 1 μm ATRA, which stimulated the differentiation of APL cells with t(15;17), was insufficient to induce differentiation, 3 μm ATRA induced terminal differentiation into granulocytes. As₂0₃ alone or in combination with ATRA induced neither differentiation nor apoptosis. However, the combination of TSA and 1 μm ATRA had a potent differentiating effect, although TSA alone had little effect. The combination of 1 μm ATRA and G‐CSF did not induce differentiation. These results indicate that APL cells with t(11;17) need a higher concentration of ATRA than those with t(15;17) to differentiate and suggest that HDAC inhibitor is a promising differentiation enhancer in APL with t(11;17).