Mitochondrial apoptosis-related gene polymorphisms are associated with responses to anthracycline-based chemotherapy in acute myeloid leukaemia

Guangqiang Meng; Mingying Li; Yuan Xia; Yuyan Wu; Yuechan Ma; Min Ji; Jingru Zhang; Jingjing Ye; Tao Sun; Chunyan Ji

doi:10.3389/fonc.2023.1179937

Mitochondrial apoptosis-related gene polymorphisms are associated with responses to anthracycline-based chemotherapy in acute myeloid leukaemia

Front Oncol. 2023 Jul 4:13:1179937. doi: 10.3389/fonc.2023.1179937. eCollection 2023.

Authors

Guangqiang Meng¹, Mingying Li¹, Yuan Xia¹, Yuyan Wu¹, Yuechan Ma¹, Min Ji¹, Jingru Zhang¹, Jingjing Ye¹, Tao Sun^{1

2}, Chunyan Ji¹

Affiliations

¹ Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
² Shandong Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, China.

Abstract

Background: 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.

Methods: We utilized the CRISPR/Cas9 screening system to find AML anthracyclines resistance related genes and several mitochondrial apoptosis-related genes, such as BCL2L11, CASP8, TP63, TP53BP2, PLAUR, SOD2, BNIP3L, and MMP9, 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.

Results: Our findings indicated that SNP rs4251864 in the PLAUR gene was associated with an increase in complete remission after anthracycline-based induction chemotherapy. rs4880 in SOD2 was associated with the response to the second course of chemotherapy, whereas rs3789068 in BCL2L11 was associated with susceptibility to AML.

Conclusions: 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.

Keywords: CRISPR/Cas9; acute myeloid leukemia; anthracyclines; mitochondrial apoptosis; single nucleotide polymorphisms.

Grants and funding

This work was supported by grants from the Distinguished Taishan Scholars in Climbing Plan (tspd20210321) and Young Taishan Scholars (tsqn201812132), the National Natural Science Foundation of China (82070160, 81873425, 82170182, 82270174), the Major Research Plan of the National Natural Science Foundation of China (91942306), the Key Program of Natural Science Foundation of Shandong Province (ZR2020KH016, ZR2020MH118), the Fundamental Research Funds for the Central Universities (2022JC012), the Independently Cultivate Innovative Teams of Jinan, Shandong Province (2021GXRC050), Multidisciplinary Research and Innovation Team of Young Scholars of Shandong University (2020QNQT007), the Clinical Practical New Technology and Development Fund of Qilu Hospital, Shandong University (2019-5), and China Postdoctoral Science Foundation (2022M711948).