CEBPA double-mutated acute myeloid leukaemia harbours concomitant molecular mutations in 76•8% of cases with TET2 and GATA2 alterations impacting prognosis
CEBPA double-mutated acute myeloid leukaemia harbours concomitant molecular mutations in 76•8% of cases with TET2 and GATA2 alterations impacting prognosis
复制标题
DOI：
10.1111/bjh.12297
复制
发表时间：
2013-06-01
影响因子：
6.5
通讯作者：
Schnittger, Susanne
中科院分区：
文献类型：
--
作者：
Grossmann, Vera;Haferlach, Claudia;Schnittger, Susanne
CEBPA突变的急性髓性白血病（AML）在目前的世界卫生组织分类中被列为临时实体。单突变（sm）和双突变（dm）病例之间的临床结局差异已被报道，因此CEBPAdm病例显示与更好的总生存期（OS）相关。除GATA 2突变外，迄今为止尚未评估CEBPAdm以外的伴随分子突变的发生率和预后影响。在这里，我们研究了95例AML CEBPAdm病例的伴随突变队列。TET 2被发现是最常见的突变，（34中心点0%）基因，其次是GATA 2（21个中心点0%），WT 1（13个中心点7%），DNMT 3A（9个中心点6%），ASXL 1（9个中心点5%），NRAS（8个中心点4%），KRAS（3个中心点2%），IDH 1/2（6个中心点3%），FLT 3-内部串联重复（6个中心点3%）、FLT 3-酪氨酸激酶结构域（2个中心点1%）、NPM 1（2个中心点1%）和RUNX 1（1/94）。TET 2基因中携带额外突变的患者显示出比TET 2野生型病例显著更差的OS（P=0中心点035），而GATA 2突变的患者显示出改善的OS（P=0中心点032）。对39例伴随突变的CEBPAdm病例进行了系列分析。在这里，我们观察到CEBPA突变在大多数病例中呈现主要致病事件（76个中心点9%）。此外，证实了CEBPAdm与CEBPAsm或CEBPA野生型病例的不同基因表达谱（GEP），而未观察到与CEBPAdm AML内的其他突变相关的GEP显著变化。
Acute myeloid leukaemia (AML) with CEBPA mutations is listed as a provisional entity in the current World Health Organization classification. A difference in clinical outcome between single- (sm) and double-mutated (dm) cases has been reported, whereupon CEBPAdm cases were shown to be associated with better overall survival (OS). The occurrence and prognostic impact of concomitant molecular mutations in addition to CEBPAdm has not been assessed until now with exception of GATA2 mutations. Here, we investigated a cohort of 95 AML CEBPAdm cases for concomitant mutations. TET2 was found to be most frequently mutated (34 center dot 0%) gene, followed by GATA2 (21 center dot 0%), WT1 (13 center dot 7%), DNMT3A (9 center dot 6%), ASXL1 (9 center dot 5%), NRAS (8 center dot 4%), KRAS (3 center dot 2%), IDH1/2 (6 center dot 3%), FLT3-internal tandem duplication (6 center dot 3%), FLT3-tyrosine kinase domain (2 center dot 1%), NPM1 (2 center dot 1%), and RUNX1 (1/94). Patients harbouring additional mutations in the TET2 gene showed significantly worse OS than TET2 wild-type cases (P=0 center dot 035), whereas GATA2-mutated patients showed improved OS (P=0 center dot 032). Serial analyses were performed for 39 CEBPAdm cases with concomitant mutations. Here, we observed that CEBPA mutations present the primary pathogenetic event in the majority of cases (76 center dot 9%). Further, a distinct gene expression profile (GEP) was confirmed for CEBPAdm versus CEBPAsm or CEBPA wild-type cases while no significant changes in GEP were observed related to additional mutations within the CEBPAdm AML.