Low frequency of MLL-partial tandem duplications in paediatric acute myeloid leukaemia using MLPA as a novel DNA screenings technique
Low frequency of MLL-partial tandem duplications in paediatric acute myeloid leukaemia using MLPA as a novel DNA screenings technique
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DOI：
10.1016/j.ejca.2010.02.019
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发表时间：
2010-07-01
影响因子：
8.4
通讯作者：
van den Heuvel-Eibrink, Marry M.
中科院分区：
文献类型：
--
作者：
Balgobind, Brian V.;Hollink, Iris H. I. M.;van den Heuvel-Eibrink, Marry M.
混合谱系白血病 (MLL) 部分串联重复 (PTD) 存在于 3-5% 的成人急性髓系白血病 (AML) 中，且与不良预后相关。在成人 AML 中，MLL-PTD 仅在 11 三体或 FLT3 内部串联重复 (FLT3-ITD) 患者中检测到。迄今为止，儿科 AML 的研究很少，并且报告 MLL-PTD 的频率存在巨大差异，经常仅利用 mRNA RT-PCR 来检测 MLL-PTD。我们研究了一大群儿科 AML (n = 276) 中 MLL-PTD 的频率以及两种不同方法的结果，即 mRNA RT-PCR 和多重连接依赖性探针扩增 (MLPA)，一种旨在检测特定 DNA 序列的拷贝数差异的方法。在一些存在 MLL 重排的患者中，检测到 MLL-PTD 转录本，但未通过 DNA-MLPA 证实，这表明与 mRNA RT-PCR 相比，DNA-MLPA 可以更准确地检测 MLL-PTD。在儿科 AML 中，7/276 名患者 (2.5%) 检测到 MLL-PTD。一名病例患有 11 三体，而其他病例则具有正常的细胞遗传学。此外，7 名患者中有 4 名显示出 FLT3-ITD，与其他 AML 病例相比显着较高 (p = 0.016)。总之，使用 DNA-MLPA 作为一种新型筛查技术，结合 mRNA RT-PCR，发现儿科 AML 中 MLL-PTD 的频率较低。需要更大规模的前瞻性研究来进一步确定 MLL-PTD 在儿科 AML 中的预后相关性。 (C) 2010 Elsevier Ltd. 保留所有权利。
Mixed-lineage leukaemia (MLL)-partial tandem duplications (PTDs) are found in 3-5% of adult acute myeloid leukaemia (AML), and are associated with poor prognosis. In adult AML, MLL-PTD is only detected in patients with trisomy 11 or internal tandem duplications of FLT3 (FLT3-ITD). To date, studies in paediatric AML are scarce, and reported large differences in the frequency of MLL-PTD, frequently utilising mRNA RT-PCR only to detect MLL-PTDs. We studied the frequency of MLL-PTD in a large cohort of paediatric AML (n = 276) and the results from two different methods, i.e. mRNA RT-PCR, and multiplex ligation-dependent probe amplification (MLPA), a method designed to detect copy number differences of specific DNA sequences. In some patients with an MLL-rearrangement, MLL-PTD transcripts were detected, but were not confirmed by DNA-MLPA, indicating that DNA-MLPA can more accurately detect MLL-PTD compared to mRNA RT-PCR. In paediatric AML, MLL-PTD was detected in 7/276 patients (2.5%). One case had a trisomy 11, while the others had normal cytogenetics. Furthermore 4 of the 7 patients revealed a FLT3-ITD, which was significantly higher compared with the other AML cases (p = 0.016). In conclusion, using DNA-MLPA as a novel screenings technique in combination with mRNA RT-PCR a low frequency of MLL-PTD in paediatric AML was found. Larger prospective studies are needed to further define the prognostic relevance of MLL-PTD in paediatric AML. (C) 2010 Elsevier Ltd. All rights reserved.