来自同源重组修复途径的RAD51和RAD50基因多态性与急性髓系白血病的疾病转归及器官毒性相关。
RAD51 and RAD50 genetic polymorphisms from homologous recombination repair pathway are associated with disease outcomes and organ toxicities in AML.
作者信息
Mohseni Alireza, Toogeh Gholamreza, Rostami Shahrbano, Faranoush Mohammad, Sharifi Mohammad Jafar
机构信息
Thalassemia Research Center, Hemoglobinopthy Institute, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Internal Medicine, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
出版信息
Blood Res. 2024 Dec 30;59(1):46. doi: 10.1007/s44313-024-00033-7.
BACKGROUND
Acute myeloid leukemia (AML) is a heterogeneous malignancy that responds to various therapies. The sensitivity of leukemia cells to chemotherapy is affected by the DNA damage response (DDR). In this study, we examined the association between RAD51 rs1801320, XRCC3 rs861539, NBS1 rs1805794, MRE11 rs569143, and RAD50 rs2299014 variants of the homologous recombination repair (HRR) pathway and AML outcomes.
MATERIAL AND METHODS
PCR-RFLP was applied for the genotyping of 67 newly diagnosed cases. We performed Sanger sequencing to confirm the results of RFLP genotyping. Outcomes and organ toxicities were collected and χ testing was performed for association analysis.
RESULTS
RAD50 variant allele carriers were protected from renal and hepatic toxicities (p = 0.024 and p = 0.045, respectively), and were associated with resistant disease (p = 0.001). RAD51 variant alleles were protected from liver toxicity (p = 0.031) and correlated with disease resistance (p = 0.012).
CONCLUSION
RAD50 rs2299014 and RAD51 rs1801320 polymorphisms may be useful for drug adjustment in AML.
背景
急性髓系白血病（AML）是一种对多种治疗有反应的异质性恶性肿瘤。白血病细胞对化疗的敏感性受DNA损伤反应（DDR）影响。在本研究中，我们检测了同源重组修复（HRR）途径的RAD51 rs1801320、XRCC3 rs861539、NBS1 rs1805794、MRE11 rs569143和RAD50 rs2299014变体与AML预后之间的关联。
材料与方法
应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对67例新诊断病例进行基因分型。我们进行桑格测序以确认RFLP基因分型结果。收集预后和器官毒性数据并进行χ检验以进行关联分析。
结果
RAD50变异等位基因携带者可免受肾毒性和肝毒性（分别为p = 0.024和p = 0.045），并与疾病耐药相关（p = 0.001）。RAD51变异等位基因可免受肝毒性（p = 0.031）并与疾病耐药相关（p = 0.012）。
结论
RAD50 rs2299014和RAD51 rs1801320多态性可能有助于AML的药物调整。
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