Histone deacetylase inhibitor but not arsenic trioxide differentiates acute promyelocytic leukaemia cells with t(11;17) in combination with all‐<i>trans</i> retinoic acid

• Kunio Kitamura

• Shinetsu Hoshi

• Mitsuru Koike

• Hitoshi Kiyoi

• Hidehiko Saito

• Tomoki Naoe

抄録

Acute promyelocytic leukaemia (APL) with t(11;17)/ PLZF‐RARα responds poorly to all‐ trans retinoic acid (ATRA) and arsenic trioxide (As 2 O 3 ), 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, As 2 0 3 , granulocyte colony‐stimulating factor (G‐CSF), HDAC inhibitor trichostatin A (TSA), or combinations of these. Although 1 μ m ATRA, which stimulated the differentiation of APL cells with t(15;17), was insufficient to induce differentiation, 3 μ m 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 μ m ATRA had a potent differentiating effect, although TSA alone had little effect. The combination of 1 μ m 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).

収録刊行物

• British Journal of Haematology

  British Journal of Haematology 108 (4), 696-702, 2000-03-29

  Wiley

キーワード

• Hematology

詳細情報

• CRID: 1360298759894260224
• NII論文ID: 30014736553
• NII書誌ID: AA00574570
• DOI: 10.1046/j.1365-2141.2000.01933.x
• ISSN: 13652141
• ISSN: 00071048
• Web Site: https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1046%2Fj.1365-2141.2000.01933.x
• Web Site: https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2141.2000.01933.x
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