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为分析3例少见SET-NUP214融合基因阳性儿童免疫球蛋白和T细胞受体基因(Ig/TR)重排模式及其临床特征,采用逆转录巢式聚合酶链反应(RT-nested PCR)检测SET-NUP214融合基因表达;采用欧洲BIOMED-2协作组设计的多重PCR体系,分析Ig/TR重排模式,并根据连接区序列设计特异性引物监测微小残留病(MRD)。结果表明,在mRNA水平3例患儿融合基因的融合位点位SET基因的第7外显子和NUP214基因的第18外显子之间。3例患儿分别诊断为混合表型急性白血病(MPAL,患儿1)、急性T淋巴细胞白血病(T-ALL,患儿2)和Ⅳ期T淋巴母细胞淋巴瘤(T-LBL,患儿3)。患儿1治疗反应极差,在造血干细胞移植后6个月复发;患儿2在诱导缓解治疗结束时(第33天)MRD>10-2,提示预后较差,在巩固治疗期死于中毒性表皮坏死溶解症导致的严重感染;患儿3在第15天时即获得血液学完全缓解(CR),第33天时MRD转阴,CR已30个月。3例患儿均检出TR基因克隆性重排,患儿1和患儿3检出TRD、TRG、TRB基因重排;患儿2只有TRD、TRB基因重排,还检出IgH以及IgKKde重排。3例患儿共检出6个TRB基因重排,均为不完全重排;TRD、TRG基因重排中,85.7%(6/7)为完全重排,14.3%(1/7)为不完全重排。结论:SET-NUP214+白血病/淋巴瘤细胞发生恶性转化的阶段可能在TRG、TRD基因重排之后、TRB基因重排开始不久。患儿1、患儿2的肿瘤细胞的不成熟程度较高,可能与预后或治疗反应差存在一定相关性。
To analyze the rearrangement patterns and clinical features of immunoglobulin and T cell receptor gene (Ig / TR) in 3 children with SET-NUP214-positive fusion protein, RT-nested PCR SET-NUP214 fusion gene was constructed. The multiplex PCR system designed by the European BIOMED-2 collaborative group was used to analyze the Ig / TR rearrangement pattern and specific primers were designed to monitor minimal residual disease (MRD). The results showed that between the exon 7 of the SET gene and the exon 18 of the NUP214 gene at the fusion site of fusion gene of 3 children with mRNA level. Three patients were diagnosed with mixed-phenotype acute leukemia (MPAL, pediatric 1), acute T-cell leukemia (T-ALL, pediatric 2) and stage IV T lymphoblastic lymphoma (T-LBL 3). Children 1 responded poorly and relapsed 6 months after hematopoietic stem cell transplantation; children 2 had MRD> 10-2 at the end of induction remission (day 33), suggesting poor prognosis and dying of consolidation therapy Serious infection due to toxic epidermal necrolysis; childhood 3 achieved hematologic complete remission (CR) on day 15, negative MRD on day 33, and CR for 30 months. TR gene rearrangement was detected in all three cases. TRD, TRG and TRB gene rearrangements were detected in children 1 and 3; TRD and TRB gene rearrangements were detected in 2 children, and IgH and IgKde were also detected row. Three TRB gene rearrangements were detected in all three cases, all of which were incomplete rearrangements. Among TRD and TRG gene rearrangements, 85.7% (6/7) were complete rearrangements and 14.3% (1/7) were not Complete rearrangement. CONCLUSIONS: The stage of malignant transformation of SET-NUP214 + leukemia / lymphoma cells may be due to the short after TRB gene rearrangement following TRG and TRD gene rearrangements. Children 1, 2 children with high degree of immaturity of tumor cells may be related to poor prognosis or treatment there is a certain correlation.