儿童急性祖B淋巴细胞白血病Ig和TCR基因重排的特征及其临床意义

目的：探讨儿童急性祖B淋巴细胞白血病（ALL）Ig和TCR基因重排与临床特征的关系及其对预后的影响。 方法：纳入2003年4月至2009年12月首都医科大学附属北京儿童医院血液肿瘤中心收治的祖B-ALL患儿，采用多重PCR联合异源双链电泳及测序方法检测IgH、IgK、IgL、TRD、TRG和TRB基因重排，其中单克隆、双克隆和寡克隆重排为阳性组，多克隆和未重排者为阴性组；各标志阳性组中根据基因克隆特性分为单克隆亚组和双/寡克隆亚组。采用卡方检验比较阳性组和阴性组临床特征的差异；Kaplan-Meier生存分析比较阳性组和阴性组、单克隆和双/寡克隆亚组无事件生存率（EFS）的差异。 结果：40例祖B-ALL患儿进入本文分析，均检测到至少1种Ig或TCR克隆性重排，IgH、IgK和IgL的检出率依次为90.0%、32.5%和10.0%；跨系TCR基因重排的比例为72.5%，TRD、TRG和TRB的检出率分别为52.5%、30.0%和17.5%。TRD基因单克隆性重排比例最高（95.2%），主要为Vδ-Dδ和Dδ-Dδ不完全重排。TRD基因重排阳性患儿白血病细胞表达CD22的频率显著低于未重排者。MLL基因重排阳性患儿未检测到TRB基因重排。各标志重排阳性组与阴性组泼尼松反应、微小残留病水平及预后差异均无统计学意义。IgH双/寡克隆亚组患儿EFS显著低于IgH单克隆亚组患儿，5年EFS分别为（58.8±12.3）%和（84.2±8.4）%，P=0.044。 结论：祖B-ALL患儿TRD基因重排与CD22表达相关，IgH单克隆性重排患儿的预后优于双/寡克隆性重排者。

The characteristics and clinical significance of immunoglobulin and T-cell receptor gene rearrangements in pediatric pro-B cell acute lymphoblastic leukemia

Objective:To investigate the correlation of immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements and clinical characteristics as well as its prognostic importance in childhood progenitor B cell acute lymphoblastic leukemia (Pro-B-ALL). Methods:The patients with Pro-B-ALL at Beijing Children's Hospital from April 2003 to December 2009 were enrolled. IgH, IgK, IgL, TRD, TRG and TRB gene rearrangements were determined by multiplex PCR, heteroduplex analysis and sequencing. Patients were divided into positive group with mono-, dual-or oligoclonal rearrangements, and negative group with polyclonal or non-rearrangement. In addition, according to clonal characteristics patients with IgH rearrangements were subgrouped into monoclonal and dual/oligoclonal. The difference of clinical features between Ig/TCR positive and negative groups were compared with Chi-square; and Kaplan-Meier method was used to analyze the difference of event-free survival (EFS) between rearrangements positive and negative groups or IgH monoclonal and dual/oligoclonal subgroups. Results:At least one clonal rearrangement of Ig or TCR was detected in 40 childhood Pro-B-ALL, with detection rate of 90.0%, 32.5% and 10.0% for IgH, IgK and IgL, respectively. Cross-lineage TCR gene rearrangements had been found in 72.5% patients, with 52.5%, 30.0% and 17.5% of cases for TRD, TRG and TRB, respectively. TRD gene rearrangement had the highest monoclonal rate with 95.2%, which was prevalent of incomplete Vδ-Dδ and Dδ-Dδ. The frequency of CD22 expression in leukemic cells with TRD gene rearrangement was significantly lower than that in patients without rearrangement. No rearrangement of TRB gene was found in patients with MLL rearrangement. No difference was found in the response to prednisone treatment, the minimal residual disease and outcome between rearrangements positive and negative patients in each Ig/TCR subgroup. The EFS of the patients with double/oligoclonal rearrangements of IgH was significantly lower than those with monoclonal rearrangement, with (58.8±12.3)% vs. (84.2±8.4)%, P=0.044. Conclusion:In patients with Pro-B-ALL, TRD gene rearrangement is associated with CD22 expression. The prognosis of patients with monoclonal IgH rearrangement is better than those with dual/oligoclonal rearrangements.