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Rad51 and Rad50 Genetic Polymorphisms From Homologous Recombination Repair Pathway Are Associated With Disease Outcomes and Organ Toxicities in Aml Publisher



Mohseni A1 ; Toogeh G2 ; Rostami S3 ; Faranoush M4 ; Sharifi MJ5
Authors

Source: Blood Research Published:2024


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. © The Author(s) 2024.
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