METHODS: Seventy one and 21 AML patients with t(8;21) and inv(16) were enrolled in this study, respectively. NPM1, CEBPA, c-KIT, IDH1/2, DNMT3A, EZH2, WT1, and CBL mutations were analyzed by direct sequencing. Patients were categorized with respect to c-KIT and WT1 mutation status, and both clinical features and prognoses were compared.
RESULTS: The incidences of FLT3 internal tandem duplication (ITD), NPM1, CEBPA, IDH1/2, DNMT3A, EZH2, and CBL mutations were low (≤5%) in CBF AML patients. However, c-KIT and WT1 mutations occurred frequently (10.9% and 13.8%, respectively). t(8;21) patients with c-KIT mutations showed significantly shorter overall survival (OS) and disease free survival (DFS) periods than those without mutations (P<0.001, for both); however, although the limited number of t(8;21) patients were analyzed, WT1 mutation status did not affect prognosis significantly. Relapse or death during follow-up occurred more frequently in t(8;21) patients carrying c-KIT mutations than in those without the mutation, although the difference was significant only in a specific patient subgroup with no WT1 mutations (P=0.014).
CONCLUSIONS: The incidences of mutations in epigenetic genes are very low in CBF AML; however, c-KIT and WT1 mutations occur more frequently than others. The poor prognostic impact of c-KIT mutation in t(8;21) AML patients only applies in a specific patient subgroup without WT1 mutations. The prognostic impact of WT1 mutation in CBF AML is not evident and further investigation is required.
方法:本研究纳入71例和21例t(8;21)和inv(16)的AML患者,分别。NPM1、CEBPA、c-KIT,IDH1/2,DNMT3A,通过直接测序分析EZH2、WT1和CBL突变。根据c-KIT和WT1突变状态对患者进行分类,并比较了临床特征和预后。
结果:FLT3内部串联重复(ITD)的发生率,NPM1、CEBPA、IDH1/2,DNMT3A,CBFAML患者的EZH2和CBL突变较低(≤5%)。然而,c-KIT和WT1突变频繁发生(10.9%和13.8%,分别)。t(8;21)有c-KIT突变的患者总生存期(OS)和无病生存期(DFS)明显短于无突变的患者(P<0.001);尽管分析了t(8;21)患者的数量有限,WT1突变状态对预后无显著影响。t(8;21)携带c-KIT突变的患者在随访期间复发或死亡的频率高于无突变的患者,尽管仅在没有WT1突变的特定患者亚组中差异显著(P=0.014).
结论:在CBFAML中,表观遗传基因突变的发生率非常低;然而,c-KIT和WT1突变比其他突变发生更频繁。t(8;21)AML患者中c-KIT突变的不良预后影响仅适用于无WT1突变的特定患者亚组。WT1突变对CBFAML的预后影响不明显,需要进一步研究。