Summary. Acute promyelocytic leukaemia (APL) with t(11;17)/PLZF-RARa responds poorly to all-trans retinoic acid (ATRA) and arsenic trioxide (As 2 O 3 ), in contrast to APL with t(15;17)/PML-RARa. Molecular studies have shown that histone deacetylase (HDAC) recruited by PLZF-RARa is associated with the ATRA resistance. Here, we analysed in vitro the differentiation of APL cells with t(11;17) using ATRA, As 2 0 3 , granulocyte colony-stimulating factor (G-CSF), HDAC inhibitor trichostatin A (TSA), or combinations of these. Although 1 mM ATRA, which stimulated the differentiation of APL cells with t(15;17), was insuf®cient to induce differentiation, 3 mM ATRA induced terminal differentiation into granulocytes. As 2 0 3 alone or in combination with ATRA induced neither differentiation nor apoptosis. However, the combination of TSA and 1 mM ATRA had a potent differentiating effect, although TSA alone had little effect. The combination of 1 mM 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).
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