Yang Lin, Liu Liang, Mi Ying-chang, Li Jian-yong, Ma Xiao-tang, Ai Xiao-fei, Qin Tie-jun, Xu Ze-feng, Wang Jian-xiang, Xiao Zhi-jian
Institute of Hematology and Blood Diseases Hospital, Tianjin 300020, China.
Zhonghua Xue Ye Xue Za Zhi. 2011 May;32(5):299-303.
To investigate the relationship between DNA homologous recombination (HR) repair genes RAD51-G135C/XRCC3-C241T polymorphisms and development of acute myeloid leukemia (AML) with recurrent chromosome translocation.
Genomic DNA was extracted from bone marrow cells of 625 de novo AML patients and peripheral blood cells of 806 patient family members and 704 unrelated volunteers. Genotypes of RAD51-G135C and XRCC3-C241T were analyzed by PCR-RFLP. Cell lines with genotypes differed from XRCC3-C241T were selected and irradiated in vitro. The CBFβ-MYH11 fusion gene was detected by TaqMan real-time PCR.
The XRCC3-C241T variant (C/T + T/T) showed 6.22-fold and 6.99-fold increase in the risk of developing the AML with inv(16)/t(16;16)/CBFβ-MYH11 as compared with the volunteer and family member controls respectively; the RAD51-G135C homozygote-type (C/C) variant showed 0.87-fold (P = 0.010) and 1.15-fold (P = 0.001) respectively increase in the risk of this subtype AML. In the irradiated group, the CBFβ-MYH11 mRNA level in HL-60 cells was 59.49 times increased than that in KG1a cells. However, the RAD51-G135C and XRCC3-C241T variants had no correlations with the risk of development of t(15;17)/PML-RARα(+)AML, t(8;21)/AML1-ETO(+) AML and 11q23 AML subtypes.
The XRCC3-C241T variant and the RAD51-G135C homozygote-type significantly increase the risk of the development of AML with inv(16)/t(16;16)/CBFβ-MYH11.
探讨DNA同源重组（HR）修复基因RAD51-G135C/XRCC3-C241T多态性与伴复发性染色体易位的急性髓系白血病（AML）发生发展的关系。
提取625例初发AML患者骨髓细胞、806例患者家庭成员外周血细胞及704例无关志愿者外周血细胞的基因组DNA。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析RAD51-G135C和XRCC3-C241T基因型。选择与XRCC3-C241T基因型不同的细胞系进行体外照射。采用TaqMan实时荧光定量PCR检测CBFβ-MYH11融合基因。
与志愿者和家庭成员对照组相比，XRCC3-C241T变异型（C/T+T/T）发生inv(16)/t(16;16)/CBFβ-MYH11 AML的风险分别增加6.22倍和6.99倍；RAD51-G135C纯合子型（C/C）变异型发生该亚型AML的风险分别增加0.87倍（P=0.010）和1.15倍（P=0.001）。照射组中，HL-60细胞的CBFβ-MYH11 mRNA水平比KG1a细胞增加59.49倍。然而，RAD51-G135C和XRCC3-C241T变异型与t(15;17)/PML-RARα(+)AML、t(8;21)/AML1-ETO(+) AML和11q23 AML亚型的发生风险无关。
XRCC3-C241T变异型和RAD51-G135C纯合子型显著增加inv(16)/t(16;16)/CBFβ-MYH11 AML的发生风险。
