文章：

HLA-DPβ1 Asp84-Lys69抗原结合特征预测儿童b细胞前体急性淋巴细胞白血病的无事件生存：来自MRC UKALL XI儿童ALL试验的结果

HLA-DPβ1 Asp84-Lys69 antigen-binding signature predicts event-free survival in childhood B-cell precursor acute lymphoblastic leukaemia: results from the MRC UKALL XI childhood ALL trial

原文发布日期：2012-07-20

DOI: 10.1038/bcj.2012.25

类型: Original Article

开放获取: 是

英文摘要：

We previously reported that children in the UKALL XI ALL trial with HLA-DP 1 and -DP 3 supertypes had significantly worse event-free survival (EFS) than children with other DP supertypes. As DP 1 and DP 3 share two of four key antigen-binding amino-acid polymorphisms (aspartic acid84–lysine69), we asked whether Asp84-Lys69 or Asp84 alone were independent prognostic indicators in childhood acute lymphoblastic leukemia (ALL). We analysed EFS in 798 UKALL XI patients, stratified by Asp84-Lys69 vs non-Asp84-Lys69, for a median follow-up of 12.5 years. Asp84-Lys69 was associated with a significantly worse EFS than non-Asp84-Lys69 (5-year EFS: Asp84-Lys69: 58.8% (95% CI (confidence of interval): 52.7–64.9%); non-Asp84-Lys69: 67.3% (63.4–71.2%); 2P=0.007). Post-relapse EFS was 10% less in Asp84-Lys69 than non-Asp84-Lys69 patients. EFS was significantly worse (P=0.03) and post-relapse EFS marginally worse (P=0.06) in patients with Asp84 compared with Gly84. These results suggest that Asp84-Lys69 predicted adverse EFS in the context of UKALL XI because of Asp84, and may have influenced post-relapse EFS. We speculate that this may be due to the recruitment of Asp84-Lys69-restricted regulatory T cells in the context of this regimen, leading to the re-emergence of residual disease. However, functional and molecular studies of the prognostic value of this and other HLA molecular signatures in other childhood ALL trials are needed.

摘要翻译： 

我们先前报道指出，在英国UKALL XI急性淋巴细胞白血病试验中，携带HLA-DP1和-DP3超型的患儿无事件生存率显著低于其他DP超型患儿。由于DP1与DP3在四个关键抗原结合氨基酸多态性位点中共享两个位点（天冬氨酸84-赖氨酸69），我们探究了Asp84-Lys69组合或单独的Asp84位点是否可作为儿童急性淋巴细胞白血病的独立预后指标。我们对798例UKALL XI试验患者进行了中位12.5年随访的无事件生存分析，按Asp84-Lys69与非Asp84-Lys69分组进行分层。结果显示，Asp84-Lys69组无事件生存率显著更差（5年无事件生存率：Asp84-Lys69组58.8%（95%置信区间：52.7-64.9%）；非Asp84-Lys69组67.3%（63.4-71.2%）；双侧P=0.007）。复发后无事件生存率在Asp84-Lys69组低出10%。与Gly84相比，Asp84患者的无事件生存率显著更差（P=0.03），复发后无事件生存率也呈现较差趋势（P=0.06）。这些结果表明，在UKALL XI试验背景下，Asp84-Lys69对不良无事件生存率的预测主要归因于Asp84位点，并可能影响复发后生存结局。我们推测这可能是由于该治疗方案引发了Asp84-Lys69限制性调节性T细胞的募集，导致残留病变重新活跃。然而，仍需通过功能和分子学研究验证该位点及其他HLA分子特征在其他儿童急淋试验中的预后价值。

原文链接：

HLA-DPβ1 Asp84-Lys69 antigen-binding signature predicts event-free survival in childhood B-cell precursor acute lymphoblastic leukaemia: results from the MRC UKALL XI childhood ALL trial