High levels of Wilms' tumor gene (wt1) mRNA in acute myeloid leukemias are associated with a worse long-term outcome
High levels of Wilms' tumor gene (wt1) mRNA in acute myeloid leukemias are associated with a worse long-term outcome
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DOI：
10.1182/blood.v90.3.1217.1217_1217_1225
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发表时间：
1997-08-01
期刊：
影响因子：
20.3
通讯作者：
Hoelzer, D
中科院分区：
文献类型：
--
作者：
Bergmann, L;Miething, C;Hoelzer, D
肿瘤抑制基因wt 1（Wilms' tumor gene）编码具有主要转录抑制特性的锌指DNA结合蛋白。由于wt 1已被证明是在绝大多数急性髓性白血病（AML）患者的表达，我们调查的相关性wt-1 mRNA表达的预后和可能的预测复发随访。研究了139例AML患者（129例新诊断的AML患者，22例首次复发的AML患者，10例首次复发的AML患者）的全部骨髓来源的原始细胞的wt 1 mRNA表达。在随访期间分析了77例患者的wt 1 mRNA表达。如前所述，进行wt 1特异性逆转录聚合酶链反应（RT-PCR），并将扩增产物目视分类为未扩增、弱扩增、中度扩增或强扩增。在代表性情况下，使用缩短的同源wt 1构建体标准品通过竞争性PCR定量PCR产物。wt 1转录本的表达与年龄、法美英（FAB）亚型、表型、核型和长期生存相关。在诊断时和首次复发时，161例样本中有124例（77%）可检测到wt 1 mRNA。Wt 1表达与年龄、既往骨髓增生异常综合征或FAB亚型无关，但在M5白血病中Wt 1转录本仅占40%（P = 0.0025）。wt 1 mRNA水平与治疗反应或由核型定义的预后组之间无相关性。长期生存率方面，高水平wt 1患者的总生存率（OS）显著低于未检测到或低水平wt 1患者。所有新诊断AML的3年OS分别为13%和38%（P = 0.038），新发AML的3年OS分别为12%和43%（P = 0.014）。在小于60岁的患者中，差异更明显。在随访期间，所有达到完全缓解的患者wt 1均为阴性。wt 1转录本的重现预测复发。这些数据表明，wt 1 mRNA的高表达与更差的长期预后相关。(C)1997年，美国血液学会。
The tumor suppressor gene wt1 (Wilms' tumor gene) encodes for a zinc finger DNA-binding protein with predominantly transcription repressing properties. Because wt1 has been shown to be expressed in the vast majority of patients with acute myeloid leukemias (AML), we investigated the relevance of wt-1 mRNA expression regarding prognosis and possible prediction of relapse during follow-up. Totally bone marrow-derived blasts of 139 AML patients (129 newly diagnosed AML patients, 22 AML patients again in first relapse, and 10 AML patients analyzed primarily in first relapse) were studied for wt1 mRNA expression. Seventy-seven patients were analyzed for wt1 mRNA expression during follow-up. wt1-specific reverse transcription-polymerase chain reaction (RT-PCR) was performed and the amplification product was visually classified as not, weakly, moderately, or strongly amplified, as described previously. PCR products were quantitated by competitive PCR using a shortened homologous wt1 construct standard in representative cases. The expression of wt1 transcripts was correlated to age, French-American-British (FAB) subtype, phenotype, karyotype, and long-term survival. wt1 mRNA was detectable in 124 of 161 (77%) samples at diagnosis and in first relapse. wt1 expression was independent from age, antecedent myelodysplastic syndrome or FAB subtype, with the exception of a significant difference in M5 leukemias showing wt1 transcripts in only 40% (P =.0025). There was no correlation between the level of wt1 mRNA and response to treatment or the prognostic groups defined by the karyotype. Concerning long-term survival, patients with high levels of wt1 had a significantly worse overall survival (OS) than those with not detectable or low levels, The 3-year OS for all newly diagnosed AMLs was 13% and 38% (P =.038), respectively, and 12% and 43% (P =.014) for de novo AMLs. The difference was more distinct in patients less than 60 years of age. During followup, all patients achieving complete remission became wt1 negative. Reoccurrence of wt1 transcripts predicted relapse. The data indicate that high expression of wt1 mRNA is associated with a worse long-term prognosis. (C) 1997 by The American Society of Hematology.