中华病理学杂志
中華病理學雜誌
중화병이학잡지
Chinese Journal of Pathology
2008年
6期
364-370
,共7页
毛峥嵘%Andreas Rosenwald%章锁江%周韧%Hans Konrad Mueller-Hermelink
毛崢嶸%Andreas Rosenwald%章鎖江%週韌%Hans Konrad Mueller-Hermelink
모쟁영%Andreas Rosenwald%장쇄강%주인%Hans Konrad Mueller-Hermelink
淋巴瘤,大细胞,弥漫型%白血病,淋巴细胞,慢性%突变%免疫表型分型%基因重排,B淋巴细胞,重链
淋巴瘤,大細胞,瀰漫型%白血病,淋巴細胞,慢性%突變%免疫錶型分型%基因重排,B淋巴細胞,重鏈
림파류,대세포,미만형%백혈병,림파세포,만성%돌변%면역표형분형%기인중배,B림파세포,중련
Lymphoma,large-cell,diffuse%Leukemia,lymphcytic,chronic%Mutation%Mutation%Immunophenotyping%Gene rearrangement,B-lymphocyte,heavy chain
目的 检测经典型Richter综合征的IgVH基因克隆重排及突变状态,分析转化前后IgVH基因的分子特征及其与预后的关系,并对可能涉及的分子机制进行初步探讨.方法 用基因扫描和测序分析IgVH基因.另外用免疫组织化学LAB-SA法检测两种肿瘤中zeta链结合蛋白激酶70(ZAP70)、p53、干扰紊调节因子(IRF)-4等可能潜在危险因子的表达,并结合随访资料进行生存率分析,筛选危险因子.结果 (1)B-CLL/DLBCL克隆相关(18/23,78.3%),克隆不相关(5/23,21.7%);(2)在16例克隆相关中,12例转化前B-CLL及转化后DLBCL携带未突变IgVH基因;(3)转化前后IgVH基因使用是非随机的,在克隆相关的病例中,B-CLL/DLBCL最常使用VH3-23、VH3-74、VH1-2,各占11.1%;(4)转化后DLBCL仅部分表达CD5(32.1%)和CD23(14.3%)及ZAP70(23.8%),绝大多数表达p53(80.6%)和IRF-4(82.6%);(5)17例转化后DLBCL患者中位生存时间为7个月;(6)统计学分析生存时间与B-CLl/DLBCL转化前后克隆相关与否、IgVH基因的突变状态、ZAP70、p53、IRF-4的表达不相关.结论 (1)转化后DLBCL中克隆相关与克隆不相关的比例为2:1;(2)克隆相关的DLBCL多由携带未突变型IgVH基因的B-CLL患者转化而来;(3)发生转化的B-CLL中IgVH基因使用的偏向性提示了抗原在转化中的可能作用;(4)转化后DLBCL与普通DLBCL在IgVH基因的使用、突变状态,免疫表型及预后的不同,提示其可能是一种新的DLBCL亚类.
目的 檢測經典型Richter綜閤徵的IgVH基因剋隆重排及突變狀態,分析轉化前後IgVH基因的分子特徵及其與預後的關繫,併對可能涉及的分子機製進行初步探討.方法 用基因掃描和測序分析IgVH基因.另外用免疫組織化學LAB-SA法檢測兩種腫瘤中zeta鏈結閤蛋白激酶70(ZAP70)、p53、榦擾紊調節因子(IRF)-4等可能潛在危險因子的錶達,併結閤隨訪資料進行生存率分析,篩選危險因子.結果 (1)B-CLL/DLBCL剋隆相關(18/23,78.3%),剋隆不相關(5/23,21.7%);(2)在16例剋隆相關中,12例轉化前B-CLL及轉化後DLBCL攜帶未突變IgVH基因;(3)轉化前後IgVH基因使用是非隨機的,在剋隆相關的病例中,B-CLL/DLBCL最常使用VH3-23、VH3-74、VH1-2,各佔11.1%;(4)轉化後DLBCL僅部分錶達CD5(32.1%)和CD23(14.3%)及ZAP70(23.8%),絕大多數錶達p53(80.6%)和IRF-4(82.6%);(5)17例轉化後DLBCL患者中位生存時間為7箇月;(6)統計學分析生存時間與B-CLl/DLBCL轉化前後剋隆相關與否、IgVH基因的突變狀態、ZAP70、p53、IRF-4的錶達不相關.結論 (1)轉化後DLBCL中剋隆相關與剋隆不相關的比例為2:1;(2)剋隆相關的DLBCL多由攜帶未突變型IgVH基因的B-CLL患者轉化而來;(3)髮生轉化的B-CLL中IgVH基因使用的偏嚮性提示瞭抗原在轉化中的可能作用;(4)轉化後DLBCL與普通DLBCL在IgVH基因的使用、突變狀態,免疫錶型及預後的不同,提示其可能是一種新的DLBCL亞類.
목적 검측경전형Richter종합정적IgVH기인극륭중배급돌변상태,분석전화전후IgVH기인적분자특정급기여예후적관계,병대가능섭급적분자궤제진행초보탐토.방법 용기인소묘화측서분석IgVH기인.령외용면역조직화학LAB-SA법검측량충종류중zeta련결합단백격매70(ZAP70)、p53、간우문조절인자(IRF)-4등가능잠재위험인자적표체,병결합수방자료진행생존솔분석,사선위험인자.결과 (1)B-CLL/DLBCL극륭상관(18/23,78.3%),극륭불상관(5/23,21.7%);(2)재16례극륭상관중,12례전화전B-CLL급전화후DLBCL휴대미돌변IgVH기인;(3)전화전후IgVH기인사용시비수궤적,재극륭상관적병례중,B-CLL/DLBCL최상사용VH3-23、VH3-74、VH1-2,각점11.1%;(4)전화후DLBCL부부분표체CD5(32.1%)화CD23(14.3%)급ZAP70(23.8%),절대다수표체p53(80.6%)화IRF-4(82.6%);(5)17례전화후DLBCL환자중위생존시간위7개월;(6)통계학분석생존시간여B-CLl/DLBCL전화전후극륭상관여부、IgVH기인적돌변상태、ZAP70、p53、IRF-4적표체불상관.결론 (1)전화후DLBCL중극륭상관여극륭불상관적비례위2:1;(2)극륭상관적DLBCL다유휴대미돌변형IgVH기인적B-CLL환자전화이래;(3)발생전화적B-CLL중IgVH기인사용적편향성제시료항원재전화중적가능작용;(4)전화후DLBCL여보통DLBCL재IgVH기인적사용、돌변상태,면역표형급예후적불동,제시기가능시일충신적DLBCL아류.
Objective To study the clonal rearrangements and mutation status of IgVH genes in classic Richter's syndrome,the relationship between molecular findings of IgVH gene and clinical outcome,and to deciper the possible molecular mechanism of transformation.Methods The clonal rearrangements and mutation status of IgVH genes were analyzed in cases of classic Richter's syndrome by Genescan and sequencing.Immunohistochemical study for zeta-chain associated protein kinase 70 kDa(ZAP70),p53 and interferon regulation factor 4(IRF-4)was also performed.Results Samples of 18 cases of B-chronic lymphocytic leukemia(B-CLL)/diffuse large B-cell lymphoma(DLBCL,78.3%)had idenfical tumor cell clones.whereas DLBCL developed as a clonally independent neoplasm in 5 patients(21.7%).Among the clonally related group, 12 cases carried unmutated VH genes in both B-CLL and DLBCL components and VH3-23,VH3-74 and VH1-2 were accounted for the B-CLL transformation to DLBCL.Immunohistochemical study showed that the transformed DLBCL expressed CD5 in 32.1%of cases,CD23 in 14.3%, ZAP70 in 23.8%,p53 in 80.6%and IRF-4 in 82.6% of the cases respectively.Follow-up data were available in 17 pailents with classic Richter's syndrome.The median survival period was 7 months.No significant difference in survival rate was obtained between the clonally related or unrelated groups,between IgVH gene mutated or unmutated groups,and between the groups with or without expression of ZAP70,p53 and IRF-4.Conclusions The ratio of clonally related transformed DLBCL from B-CLL to clonally unrelated DLBCL is 2:1.Clonal transformation to DLBCL predominantly occurs in B-CLL patients carrying unmutated IgVH genes.The biased IgVH gene usage suggests antigens are involved in classic Richter's syndrome.Molecular differences of IgVH genes and very poor clinical outcome of this group of transformed DLBCL indicate that there cases may be regarded as a distinct subset of DLBCL.
