全反式维甲酸是第一个治疗急性早幼粒细胞白血病(APL)的诱导分化药物，然而仍有部分APL病人对维甲酸耐药，cAMP缺失是其耐药原因之一，但维甲酸诱导APL产生cAMP的机制尚不清楚。在前期工作中，我们发现TMEM64可促进维甲酸诱导APL细胞产生cAMP和细胞分化。本研究拟以APL细胞株和患者原代细胞为研究对象，通过慢病毒干扰或过表达TMEM64，研究TMEM64在维甲酸诱导APL细胞产生cAMP和细胞分化中的作用，以及在维甲酸敏感和耐药的APL患者细胞中证实TMEM64的生物学作用。通过研究：1）TMEM64对内质网钙离子信号、SERCA活性、CaMK活性、cAMP产生的影响；2）TMEM64与维甲酸之间的结合，以及TMEM64在维甲酸诱导的G蛋白和PLCβ活化中的作用，拟揭示维甲酸诱导cAMP产生和细胞分化的分子机制，为耐药APL患者提供个体化的治疗和耐药机制研究奠定理论和实验基础。

All-trans retinoic acid (ATRA) is the first differentiation-inducing agent for curing acute promyelocytic leukemia (APL). However，partial APL patients still are resistant to ATRA, deficient cAMP is one reason of retinoic acid resistance, but its mechanism of cAMP generation induced by ATRA remains unclear. In previous work, we discover that TMEM64 could promote APL cell differentiation and cAMP generation induced by ATRA. This investigation takes APL cell lines and patients’ primary cells as research subjects. Through overexpressing or interfering with TMEM64 by lentiviral vector, we intend to investigate the effects of TMEM64 on cAMP generation and cell differentiation induced by ATRA in APL cells, and to confirm the biological functions of TMEM64 in APL primary cell. By studying the effects of TMEM64 on calcium signal, SERCA activity, CaMK activity, cAMP generation, and then studying the bind capacity between TMEM64 and ATRA which activates G protein and PLCβ signal pathway, it could reveal the molecular mechanism of cAMP generation and APL cell differentiation induced by ATRA. This project could provide theoretical and experimental basis for APL individualized treatment and drug resistance study.