Alireza Mohseni, Gholamreza Toogeh, Shahrbano Rostami, Mohammad Faranoush, Mohammad Jafar Sharifi
{"title":"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。","authors":"Alireza Mohseni, Gholamreza Toogeh, Shahrbano Rostami, Mohammad Faranoush, Mohammad Jafar Sharifi","doi":"10.1007/s44313-024-00033-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Material and methods: </strong>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<sup>2</sup> testing was performed for association analysis.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>RAD50 rs2299014 and RAD51 rs1801320 polymorphisms may be useful for drug adjustment in AML.</p>","PeriodicalId":46224,"journal":{"name":"Blood Research","volume":"59 1","pages":"46"},"PeriodicalIF":2.3000,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685162/pdf/","citationCount":"0","resultStr":"{\"title\":\"RAD51 and RAD50 genetic polymorphisms from homologous recombination repair pathway are associated with disease outcomes and organ toxicities in AML.\",\"authors\":\"Alireza Mohseni, Gholamreza Toogeh, Shahrbano Rostami, Mohammad Faranoush, Mohammad Jafar Sharifi\",\"doi\":\"10.1007/s44313-024-00033-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Material and methods: </strong>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<sup>2</sup> testing was performed for association analysis.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>RAD50 rs2299014 and RAD51 rs1801320 polymorphisms may be useful for drug adjustment in AML.</p>\",\"PeriodicalId\":46224,\"journal\":{\"name\":\"Blood Research\",\"volume\":\"59 1\",\"pages\":\"46\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-12-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685162/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Blood Research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1007/s44313-024-00033-7\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s44313-024-00033-7","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
RAD51 and RAD50 genetic polymorphisms from homologous recombination repair pathway are associated with disease outcomes and organ toxicities in AML.
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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