中华血液学杂志
中華血液學雜誌
중화혈액학잡지
Chinese Journal of Hematology
2011年
5期
299-303
,共5页
杨琳%刘亮%秘营昌%李建勇%马晓瑭%艾晓非%秦铁军%徐泽锋%王建祥%肖志坚
楊琳%劉亮%祕營昌%李建勇%馬曉瑭%艾曉非%秦鐵軍%徐澤鋒%王建祥%肖誌堅
양림%류량%비영창%리건용%마효당%애효비%진철군%서택봉%왕건상%초지견
多态性,单核苷酸%白血病,非淋巴细胞,急性%易位,遗传%疾病遗传易感性
多態性,單覈苷痠%白血病,非淋巴細胞,急性%易位,遺傳%疾病遺傳易感性
다태성,단핵감산%백혈병,비림파세포,급성%역위,유전%질병유전역감성
Polymorphism,single nucleotide%Leukemia,nonlymphocytic,acute%Translocation,genetic%Genetic predisposition to disease
目的 探讨DNA同源重组修复基因RAD51-G135C和XRCC3-C241T多态性与伴重现染色体易位急性髓系白血病(AML)发生的关系.方法 共收集625例初治原发性AML患者的骨髓、806名患者一级亲属和704名与患者无血缘关系正常人的外周血样本,常规提取基因组DNA.用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法分析RAD51-G135C和XRCC3-C241T基因多态性.选取XRCC3-C241T不同基因型细胞系进行体外照射,用TaqMan实时定量PCR法检测CBFβ-MYH11融合基因mRNA的相对表达量.结果 同正常人和一级亲属比较,XRCC3-C241T变异基因型(C/T+T/T)能明显提高inv(16)/t(16;16)/CBFβ-MYH11(+)AML的发病风险,风险值分别提高了6.22倍(P<0.001)和6.99倍(P<0.001);同正常人和一级亲属比较,RAD51-G135C纯合变异基因型(C/C)亦能明显提高inv(16)/t(16;16)/CBFβ-MYH11(+)AML的发病风险,风险值分别提高了0.87倍(P=0.010)和1.15倍(P=0.001).经照射后,XRCC3-C241T纯合变异型HL-60细胞系CBFβ-MYH11融合基因mRNA表达量是野生型KG1a细胞系的59.49倍.RAD51-G135C和XRCC3-C241T多态性位点基因型与t(15;17)/PML-RARα(+)AML、t(8;21)/AMLI-ETO(+)AML和11q23异常AML发生风险无明显相关性.结论 XRCC3-C241T变异基因型和RAD51-G135C纯合变异基因型可显著增高inv(16)/t(16;16)/CBFβ-MYH11(+)AML发生的风险.
目的 探討DNA同源重組脩複基因RAD51-G135C和XRCC3-C241T多態性與伴重現染色體易位急性髓繫白血病(AML)髮生的關繫.方法 共收集625例初治原髮性AML患者的骨髓、806名患者一級親屬和704名與患者無血緣關繫正常人的外週血樣本,常規提取基因組DNA.用聚閤酶鏈反應-限製性片段長度多態性(PCR-RFLP)方法分析RAD51-G135C和XRCC3-C241T基因多態性.選取XRCC3-C241T不同基因型細胞繫進行體外照射,用TaqMan實時定量PCR法檢測CBFβ-MYH11融閤基因mRNA的相對錶達量.結果 同正常人和一級親屬比較,XRCC3-C241T變異基因型(C/T+T/T)能明顯提高inv(16)/t(16;16)/CBFβ-MYH11(+)AML的髮病風險,風險值分彆提高瞭6.22倍(P<0.001)和6.99倍(P<0.001);同正常人和一級親屬比較,RAD51-G135C純閤變異基因型(C/C)亦能明顯提高inv(16)/t(16;16)/CBFβ-MYH11(+)AML的髮病風險,風險值分彆提高瞭0.87倍(P=0.010)和1.15倍(P=0.001).經照射後,XRCC3-C241T純閤變異型HL-60細胞繫CBFβ-MYH11融閤基因mRNA錶達量是野生型KG1a細胞繫的59.49倍.RAD51-G135C和XRCC3-C241T多態性位點基因型與t(15;17)/PML-RARα(+)AML、t(8;21)/AMLI-ETO(+)AML和11q23異常AML髮生風險無明顯相關性.結論 XRCC3-C241T變異基因型和RAD51-G135C純閤變異基因型可顯著增高inv(16)/t(16;16)/CBFβ-MYH11(+)AML髮生的風險.
목적 탐토DNA동원중조수복기인RAD51-G135C화XRCC3-C241T다태성여반중현염색체역위급성수계백혈병(AML)발생적관계.방법 공수집625례초치원발성AML환자적골수、806명환자일급친속화704명여환자무혈연관계정상인적외주혈양본,상규제취기인조DNA.용취합매련반응-한제성편단장도다태성(PCR-RFLP)방법분석RAD51-G135C화XRCC3-C241T기인다태성.선취XRCC3-C241T불동기인형세포계진행체외조사,용TaqMan실시정량PCR법검측CBFβ-MYH11융합기인mRNA적상대표체량.결과 동정상인화일급친속비교,XRCC3-C241T변이기인형(C/T+T/T)능명현제고inv(16)/t(16;16)/CBFβ-MYH11(+)AML적발병풍험,풍험치분별제고료6.22배(P<0.001)화6.99배(P<0.001);동정상인화일급친속비교,RAD51-G135C순합변이기인형(C/C)역능명현제고inv(16)/t(16;16)/CBFβ-MYH11(+)AML적발병풍험,풍험치분별제고료0.87배(P=0.010)화1.15배(P=0.001).경조사후,XRCC3-C241T순합변이형HL-60세포계CBFβ-MYH11융합기인mRNA표체량시야생형KG1a세포계적59.49배.RAD51-G135C화XRCC3-C241T다태성위점기인형여t(15;17)/PML-RARα(+)AML、t(8;21)/AMLI-ETO(+)AML화11q23이상AML발생풍험무명현상관성.결론 XRCC3-C241T변이기인형화RAD51-G135C순합변이기인형가현저증고inv(16)/t(16;16)/CBFβ-MYH11(+)AML발생적풍험.
Objective 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. Methods 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. Results 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 11 q23 AML subtypes. Conclusion 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.
