《肿瘤瞭望》：全反式维甲酸耐药在中国很常见。日本的情况怎么样？

　　Takeshita教授: ATRA耐药对于急性早幼粒细胞白血病（APL）的治疗是非常重要的一个问题。耐药产生的机制如下：1. 细胞色素P450降低了ATRA发挥作用的药物浓度；2. CRABP（细胞视黄酸结合蛋白）的出现，减少了ATRA的胞浆水平；3. PML基因和RAR基因存在点突变。前二个机制导致的耐药可以通过合成的类视黄醇样的药物他米巴罗汀来治疗，点突变导致的耐药则可以采用ATO进行治疗。在日本对ATRA产生部分耐药的患者会接受他米巴罗汀治疗，对ATAR完全耐药的患者则接受ATO的治疗。

ATRA resistance is very important in the treatment of acute promyelocytic leukemia (APL). There are several mechanisms of resistance. One is the effect of cytochrome P450 which decreases the threshold level of ATRA. The second is the development of CRABP (cellular retinoic acid binding protein). This decreases cytoplasmic levels of ATRA. Thirdly， there are point mutations of the PML gene and RAR gene. The first two can be managed with synthetic retinoids like tamibarotene. The point mutations are managed with ATO (arsenic trioxide). In Japan， patients who are partially resistant to ATRA will receive tamibarotene. Patients with complete resistance to ATRA are treated with ATO.

　　《肿瘤瞭望》：: 您谈到的上述治疗是否能够治愈APL?

　　Takeshita教授: APL有许多治愈性方法可选，对于早期APL采用药物治疗有效，药物可以是ATO联合ATRA，或是ATO联合他米巴罗汀，这些药物都可以达到治愈APL。

There are many opinions on how to cure APL. The drugs we use are effective in early APL， either ATO plus ATRA or ATO plus tamibarotene. These drugs are effective in the cure of APL.

　　《肿瘤瞭望》： 您能谈谈他米巴罗汀的疗效吗？

　　Takeshita教授：他米巴罗汀是由东京大学的Shudo博士合成的一种类视黄醇样的药物。它显著诱导APL细胞分化，且不与视黄酸受体γ结合，与视黄酸结合蛋白结合能力也极微弱。它对抗光、热和氧化的能力也很强，其稳定性超过了ATRA，他米巴罗汀的疗效是ATRA的5倍。

Tamibarotene is a synthetic retinoid made by Dr Shudo from Tokyo University. It shows strong differentiation of the APL cell and does not bind to retinoic acid receptor gamma and binds weakly to retinoic acid binding protein. It is more stable against light， heat and oxidation than ATRA and tamibarotene is five times more potent than ATRA.