RAD51 and RAD50 genetic polymorphisms from homologous recombination repair pathway are associated with disease outcomes and organ toxicities in AML.

IF 2.3 Q2 HEMATOLOGY

Blood Research Pub Date : 2024-12-30 DOI:10.1007/s44313-024-00033-7

Alireza Mohseni, Gholamreza Toogeh, Shahrbano Rostami, Mohammad Faranoush, Mohammad Jafar Sharifi

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引用次数: 0

Abstract

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 χ² 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.

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同源重组修复途径的RAD51和RAD50基因多态性与AML的疾病结局和器官毒性相关。

背景：急性髓性白血病（AML）是一种异质性恶性肿瘤，对多种治疗有反应。白血病细胞对化疗的敏感性受DNA损伤反应（DDR）的影响。在这项研究中，我们检测了同源重组修复（HRR）途径的RAD51 rs1801320、XRCC3 rs861539、NBS1 rs1805794、MRE11 rss569143和RAD50 rs2299014变体与AML结果之间的关系。材料与方法：应用PCR-RFLP对67例新诊断病例进行基因分型。我们进行Sanger测序以确认RFLP基因分型结果。收集结果和器官毒性，采用χ2检验进行相关性分析。结果：RAD50变异等位基因携带者免受肾和肝毒性（p = 0.024和p = 0.045分别），并与耐药疾病相关（p = 0.001）。RAD51变异等位基因免受肝毒性影响（p = 0.031），并与抗病性相关（p = 0.012）。结论：RAD50 rs2299014和RAD51 rs1801320多态性可能对AML患者的药物调节有重要意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Blood Research HEMATOLOGY-

CiteScore

3.70

自引率

0.00%

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