Meng Guangqiang, Li Mingying, Xia Yuan, Wu Yuyan, Ma Yuechan, Ji Min, Zhang Jingru, Ye Jingjing, Sun Tao, Ji Chunyan
Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Shandong Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, China.
Front Oncol. 2023 Jul 4;13:1179937. doi: 10.3389/fonc.2023.1179937. eCollection 2023.
Although anthracyclines are the first-line chemotherapy drugs for treating non-M3 acute myeloid leukaemia (AML), their efficacy remains limited. It is important to identify factors that influence the efficacy of anthracyclines against AML. Mitochondrial apoptosis-related genes play significant roles in the pathogenesis, treatment, and prognosis of AML.
We utilized the CRISPR/Cas9 screening system to find AML anthracyclines resistance related genes and several mitochondrial apoptosis-related genes, such as , , , , , , , and , were screened out. Then, DNA from 279 patients with AML and 321 healthy individuals were extracted and the contributions of single nucleotide polymorphisms (SNPs) within these genes to the patient's chemotherapy response, susceptibility to AML, and overall survival were investigated.
Our findings indicated that SNP rs4251864 in the gene was associated with an increase in complete remission after anthracycline-based induction chemotherapy. rs4880 in was associated with the response to the second course of chemotherapy, whereas rs3789068 in was associated with susceptibility to AML.
Our results about the association of SNPs in mitochondrial apoptosis-related genes with the response to anthracycline-based chemotherapy in AML provide an important reference for predicting the treatment outcomes in patients with this disease.
尽管蒽环类药物是治疗非M3急性髓系白血病（AML）的一线化疗药物，但其疗效仍然有限。识别影响蒽环类药物治疗AML疗效的因素很重要。线粒体凋亡相关基因在AML的发病机制、治疗和预后中起重要作用。
我们利用CRISPR/Cas9筛选系统寻找与AML蒽环类药物耐药相关的基因，并筛选出了几个线粒体凋亡相关基因，如 、 、 、 、 、 、 和 。然后，提取了279例AML患者和321例健康个体的DNA，并研究了这些基因内单核苷酸多态性（SNP）对患者化疗反应、AML易感性和总生存期的影响。
我们的研究结果表明， 基因中的SNP rs4251864与基于蒽环类药物的诱导化疗后完全缓解率的增加有关。 基因中的rs4880与第二疗程化疗的反应有关，而 基因中的rs3789068与AML易感性有关。
我们关于线粒体凋亡相关基因中的SNP与AML患者基于蒽环类药物化疗反应之间关联的结果，为预测该疾病患者的治疗结果提供了重要参考。
