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亚组分析可优化急性髓系白血病异基因造血干细胞移植后 WT1 表达的复发预测截断值。

Subgroup Analysis Can Optimize the Relapse-Prediction Cutoff Value for WT1 Expression After Allogeneic Hematologic Stem Cell Transplantation in Acute Myeloid Leukemia.

机构信息

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, People's Republic of China.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, People's Republic of China.

出版信息

J Mol Diagn. 2020 Feb;22(2):188-195. doi: 10.1016/j.jmoldx.2019.10.003. Epub 2019 Nov 18.

Abstract

High WT1 expression after allogeneic hematologic stem cell transplantation (allo-HSCT) can strongly predict relapse in acute myeloid leukemia (AML). However, the cutoff values obtained have been inconsistent. Precise cutoff values may be optimized through subtype analysis; the RUNX1-RUNX1T1 fusion transcript provides an ideal reference. RUNX1-RUNX1T1 and WT1 transcript levels were simultaneously measured in 1299 bone marrow samples serially collected from 176 t(8;21) AML patients after allo-HSCT. The upper limit of the normal bone marrow WT1 level was 0.6%, which we previously reported to be the cutoff value for significant relapse prediction in AML as a whole. WT1 cutoff values of 0.6%, 1.2%, and 1.8% significantly differentiated patients in relapse after allo-HSCT. Nonetheless, patients with WT1 levels of 0.6% to 1.2% and those with levels of >1.2% and 1.8% after HSCT had rates of cumulative incidence of relapse similar to those with a continuous WT1 level of ≤0.6%, and both were significantly lower than that in patients with a WT1 level of >1.8%. WT1 expression was significantly related to RUNX1-RUNX1T1 transcript levels at WT1 levels of >1.8% but not at levels of 0.6% to 1.2% or >1.2% to 1.8%. Therefore, subgroup analysis can optimize the relapse-prediction cutoff value of WT1 expression. A cutoff level of 1.8% more accurately differentiates t(8;21) AML patients in relapse after allo-HSCT than does a cutoff level of 0.6%.

摘要

异基因造血干细胞移植(allo-HSCT)后高 WT1 表达可强烈预测急性髓系白血病(AML)的复发。然而,获得的截止值并不一致。通过亚型分析可以优化精确的截止值;RUNX1-RUNX1T1 融合转录本提供了一个理想的参考。在 allo-HSCT 后,对 176 例 t(8;21)AML 患者连续采集的 1299 例骨髓样本同时测量 RUNX1-RUNX1T1 和 WT1 转录本水平。我们之前报道过,骨髓 WT1 水平的正常上限为 0.6%,是整个 AML 显著复发预测的截止值。WT1 截止值为 0.6%、1.2%和 1.8%可显著区分 allo-HSCT 后复发的患者。尽管如此,WT1 水平为 0.6%至 1.2%和 >1.2%至 1.8%的患者的累积复发发生率与 WT1 水平连续 ≤0.6%的患者相似,两者均显著低于 WT1 水平 >1.8%的患者。WT1 表达与 RUNX1-RUNX1T1 转录本水平显著相关,WT1 水平 >1.8%时,但在 0.6%至 1.2%或 >1.2%至 1.8%时则不然。因此,亚组分析可以优化 WT1 表达的复发预测截止值。与截止值为 0.6%相比,截止值为 1.8%更能准确地区分 allo-HSCT 后复发的 t(8;21)AML 患者。

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