WT1 gene expression:: an excellent tool for monitoring minimal residual disease in 70% of acute myeloid leukaemia patients -: results from a single-centre study
WT1 gene expression:: an excellent tool for monitoring minimal residual disease in 70% of acute myeloid leukaemia patients -: results from a single-centre study
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DOI：
10.1111/j.1365-2141.2004.04952.x
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发表时间：
2004-06-01
影响因子：
6.5
通讯作者：
Hokland, P
中科院分区：
文献类型：
--
作者：
Ostergaard, M;Olesen, LH;Hokland, P
急性髓性白血病（AML）诱导化疗后，在达到完全缓解（CR）的患者中灵敏地测定微小残留病（MRD）应能够检测早期复发，并允许在比明显复发更有利的阶段进行干预。我们用实时定量聚合酶链反应（RQ-PCR）检测了133例初诊AML患者外周血和骨髓中Wilms肿瘤基因（WT 1）的表达水平，并与健康志愿者进行了比较。在诊断时，133例患者中有118例（89%）的WT 1水平超过正常表达，并且足以在诱导治疗后的133例患者中的98例（74%）中检测到WT 1降低至少1000倍。在38例患者中同时监测融合转录物（PML-RAR α、AML 1-ETO、MLL-MLL、CBFbeta-MYH 11或DEK-CAN），发现WT 1与融合转录物水平之间存在不同的关系，与融合转录物相比，AML 1-ETO组显示WT 1水平显著较低。在32例纵向分析有复发和增加WT 1水平之间的密切一致性。18例患者中有18例的WT 1和融合转录本的平行纵向监测显示密切相关。我们的结论是，通过RQ-PCR的WT 1表达可以作为一种工具来检测MRD在大多数融合转录阴性AML患者。
Following induction chemotherapy for acute myeloid leukaemia (AML), sensitive determination of minimal residual disease (MRD) in patients achieving complete remission (CR) should enable the detection of early relapse and allow intervention at a more favourable stage than at overt relapse. We have determined the expression levels of the Wilms' tumour gene (WT1) by real-time quantitative polymerase chain reaction (RQ-PCR) in peripheral blood and bone marrow in 133 newly diagnosed AML patients and compared them with those in healthy volunteers. At diagnosis, the WT1 level exceeded normal expression in 118 of 133 (89%) patients, and was high enough to allow for detection of a WT1 decrease of least 1000-fold in 98 of 133 (74%) patients following induction therapy. Concomitant monitoring of fusion transcripts (PML-RARalpha, AML1-ETO, MLL-MLL, CBFbeta-MYH11, or DEK-CAN) in 38 patients identified different relationships between WT1 and fusion transcript levels, the AML1-ETO group showing remarkably low levels of WT1 compared with fusion transcript. In 32 patients analysed longitudinally there was close concordance between relapse and increased WT1 levels. Parallel longitudinal monitoring of WT1 and fusion transcript showed close correlation in 18 of 18 patients. We conclude that WT1 expression by RQ-PCR may be employed as a tool to detect MRD in the majority of fusion transcript-negative AML patients.