The main challenges in treating acute promyelocytic leukemia (APL) are currently early mortality, relapse, refractory disease after induction therapy, and drug resistance to ATRA and ATO. In this study, a computational chemogenomics approach was used to identify new molecular targets and drugs for APL treatment. The transcriptional profiles induced by APL were compared with those induced by genetic or chemical perturbations. The genes that can reverse the transcriptional profiles induced by APL when perturbed were considered to be potential therapeutic targets for APL. Drugs targeting these genes or proteins are predicted to be able to treat APL if they can reverse the APL-induced transcriptional profiles. To improve the target identification accuracy of the above correlation method, we plotted the functional protein association networks of the predicted targets by STRING. The results determined PML, RARA, SPI1, HDAC3, CEBPA, NPM1, ABL1, BCR, PTEN, FOS, PDGFRB, FGFR1, NUP98, AFF1, and MEIS1 to be top candidates. Interestingly, the functions of PML, RARA, HDAC3, CEBPA, NPM1, ABL, and BCR in APL have been previously reported in the literature. This is the first chemogenomics analysis predicting potential APL drug targets, and the findings could be used to guide the design of new drugs targeting refractory and recurrent APL.

中文翻译：

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药物靶点的化学基因组学分析，用于治疗急性早幼粒细胞白血病。

目前治疗急性早幼粒细胞白血病（APL）的主要挑战是早期死亡率，复发，诱导治疗后的难治性疾病以及对ATRA和ATO的耐药性。在这项研究中，使用了一种计算化学基因组学方法来确定用于APL治疗的新分子靶标和药物。将APL诱导的转录谱与遗传或化学扰动诱导的转录谱进行比较。被干扰时能逆转APL诱导的转录谱的基因被认为是APL的潜在治疗靶标。如果靶向这些基因或蛋白质的药物可以逆转APL诱导的转录谱，则可以治疗APL。为了提高上述相关方法的目标识别精度，我们通过STRING绘制了预测靶标的功能蛋白缔合网络。结果确定PML，RARA，SPI1，HDAC3，CEBPA，NPM1，ABL1，BCR，PTEN，FOS，PDGFRB，FGFR1，NUP98，AFF1和MEIS1是最佳候选者。有趣的是，APL中的PML，RARA，HDAC3，CEBPA，NPM1，ABL和BCR的功能先前已在文献中进行了报道。这是第一个预测潜在APL药物靶点的化学基因组学分析，该发现可用于指导针对难治性和复发性APL的新药的设计。