EVI1 overexpression in distinct subtypes of pediatric acute myeloid leukemia
EVI1 overexpression in distinct subtypes of pediatric acute myeloid leukemia
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DOI：
10.1038/leu.2010.47
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发表时间：
2010-05-01
期刊：
影响因子：
11.4
通讯作者：
van den Heuvel-Eibrink, M. M.
中科院分区：
文献类型：
--
作者：
Balgobind, B. V.;Lugthart, S.;van den Heuvel-Eibrink, M. M.
位于染色体 3q26 的亲嗜性病毒整合 1 (EVI1) 基因 (EVI1+) 的过度表达与成人急性髓系白血病 (AML) 的不良后果相关。在儿童 AML 中，3q26 异常很少见，EVI1 的作用尚不清楚。我们使用基因表达谱和 RQ-PCR 研究了 228 个儿童 AML 样本中的 EVI1+。 EVI1+ 在 20/213 (9%) 的初发 AML 儿童中发现，在 4/8 的继发 AML 儿童中发现。它主要存在于 MLL 重排 AML (13/47)、单体 7 (2/3) 或 FAB M6/7 (6/10) 中，并且与核心结合因子 AML、t(15;17) 和 NPM1 突变相互排斥。进行荧光原位杂交 (FISH) 来检测隐秘的 3q26 异常。然而，EVI1+ 患者均未出现 3q26 结构改变。尽管观察到 EVI1+ 和 EVI1 儿童 AML 的 4 年 pEFS 存在显着差异（28%+/- 11 vs 44%+/- 4，P=0.04），但多变量分析并未将 EVI1+ 确定为独立的预后因素。我们得出的结论是，EVI1+ 存在于大约 10% 的儿童 AML 中。尽管 EVI1+ 不是一个独立的预后因素，但它主要存在于与中等至不良预后相关的儿科 AML 亚型中。进一步的研究应该解释 EVI1+ 在这些病例中疾病生物学中的作用。值得注意的是，在 EVI1+ 儿童 AML 中未发现 3q26 异常。白血病 (2010) 24, 942-949; doi：10.1038/leu.2010.47； 2010 年 4 月 1 日在线发布
Overexpression of the ecotropic virus integration-1 (EVI1) gene (EVI1+), localized at chromosome 3q26, is associated with adverse outcome in adult acute myeloid leukemia (AML). In pediatric AML, 3q26 abnormalities are rare, and the role of EVI1 is unknown. We studied 228 pediatric AML samples for EVI1+ using gene expression profiling and RQ-PCR. EVI1+ was found in 20/213 (9%) of children with de novo AML, and in 4/8 with secondary AML. It was predominantly found in MLL-rearranged AML (13/47), monosomy 7 (2/3), or FAB M6/7 (6/10), and mutually exclusive with core-binding factor AML, t(15;17), and NPM1 mutations. Fluorescent in situ hybridization (FISH) was performed to detect cryptic 3q26 abnormalities. However, none of the EVI1+ patients harbored structural 3q26 alterations. Although significant differences in 4 years pEFS for EVI1+ and EVI1 pediatric AML were observed (28%+/- 11 vs 44%+/- 4, P=0.04), multivariate analysis did not identify EVI1+ as an independent prognostic factor. We conclude that EVI1+ can be found in similar to 10% of pediatric AML. Although EVI1+ was not an independent prognostic factor, it was predominantly found in subtypes of pediatric AML that are related with an intermediate to unfavorable prognosis. Further research should explain the role of EVI1+ in disease biology in these cases. Remarkably, no 3q26 abnormalities were identified in EVI1+ pediatric AML. Leukemia (2010) 24, 942-949; doi:10.1038/leu.2010.47; published online 1 April 2010