Ishitsuka K, Hanada S, Suzuki S, Utsunomiya A, Chyuman Y, Takeuchi S, Takeshita T, Shimotakahara S, Uozumi K, Makino T, Arima T
Second Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Japan.
Br J Haematol. 1998 Dec;103(3):721-8. doi: 10.1046/j.1365-2141.1998.01068.x.
Adult T-cell leukaemia (ATL) is difficult to cure using conventional therapies. Recently the therapeutic possibility of retinoic acids (RA) has been reported. In this study, suppression of in vitro growth of human T-cell leukaemia virus type I (HTLV-I) infected T-cell lines and fresh ATL cells by arsenic trioxide (As2O3) were evaluated by comparison with a series of RA derivatives. Proliferation of four HTLV-I-infected T-cell lines was significantly reduced within 72 h by 1.0 micromol/l As2O3. Growth of two out of four HTLV-I-infected T-cell lines was also inhibited by 1.0 micromol/l RA, but to a lesser extent than by As2O3. The mechanism of this growth inhibition was due to the induction of apoptosis. Apoptosis was also induced in fresh ATL cells from patients by AS2O3, but far less by RA. As described in patients with acute promyelocytic leukaemia, 1.0 micromol/l of As2O3 can be safely achieved in the serum of patients; however, it is difficult to maintain this concentration of RA. In conclusion, As2O3 has therapeutic potential for the treatment of ATL and may be far more clinically beneficial than RA.
成人T细胞白血病（ATL）采用传统疗法难以治愈。最近有报道称视黄酸（RA）具有治疗潜力。在本研究中，通过与一系列RA衍生物进行比较，评估了三氧化二砷（As2O3）对人I型T细胞白血病病毒（HTLV-I）感染的T细胞系和新鲜ATL细胞体外生长的抑制作用。1.0微摩尔/升的As2O3在72小时内可显著降低四种HTLV-I感染的T细胞系的增殖。1.0微摩尔/升的RA也可抑制四种HTLV-I感染的T细胞系中的两种的生长，但程度低于As2O3。这种生长抑制的机制是由于诱导了细胞凋亡。As2O3也可诱导患者新鲜ATL细胞发生凋亡，但RA诱导的凋亡要少得多。正如急性早幼粒细胞白血病患者的情况一样，患者血清中可以安全地达到1.0微摩尔/升的As2O3浓度；然而，很难维持这种RA浓度。总之，As2O3对ATL治疗具有潜在的治疗潜力，在临床上可能比RA更有益。
