髓过氧化物酶表达与急性髓系白血病基因突变和预后的相关性研究

Correlation between myeloperoxidase expression and gene alterations and prognosis in acute myeloid leukemia

目的观察髓过氧化物酶(MPO)在急性髓系白血病(AML)中的表达,探讨其与AML临床特征、基因突变、疗效和预后的关系。方法回顾性分析233例初诊AML患者骨髓中原始细胞MPO表达的阳性率,根据MPO表达率不同将其分为MPO低表达组(MPO≤70%)与MPO高表达组(MPO>70%),并对两组患者的临床特征、基因突变、疗效和预后进行比较。结果①233例AML患者中MPO低表达组121例(51.9%),MPO高表达组112例(48.1%)。NCCN预后良好组患者多为MPO高表达(χ^2=32.773,P<0.001),而MPO低表达与预后不良核型相关(χ^2=7.078,P=0.008)。②MPO低表达组DNMT3A基因(χ^2=6.905,P=0.009)、RNA剪接复合物相关基因(SF3B1/SRSF2/U2AF1)(χ^2=5.246,P=0.022)、RUNX1基因(χ^2=4.577,P=0.032)、ASXL1基因(χ^2=7.951,P=0.005)及TP53基因(P=0.004)突变发生率明显高于MPO高表达组,而C-KIT基因(χ^2=8.936,P=0.003)及CEBPA基因(χ^2=12.340,P<0.001)突变更多见于MPO高表达组,尤其CEBPA双位点突变。③MPO低表达组首次诱导治疗缓解(CR1)率为38.8%,MPO高表达组为68.1%,差异有统计学意义(χ^2=15.197,P<0.001)。多因素分析显示MPO低表达是影响患者CR1的独立危险因素。④MPO低表达组患者的2年总生存(OS)率及无进展生存(PFS)率均明显低于高表达组(18.0%对89.4%和11.5%对56.7%),差异有统计学意义(χ^2分别为15.212和17.016,P值均<0.001)。Cox模型多因素分析显示MPO低表达是影响患者OS及PFS的独立预后不良指标。⑤正常核型AML中,MPO低表达组患者OS和PFS差于MPO高表达组(2年OS率:31.1%对83.7%,χ^2=2.895,P=0.089;2年PFS率:18.8%对45.8%,χ^2=5.068,P=0.024)。结论不同MPO表达的AML具有独特的基因突变谱;MPO低表达是影响AML患者CR1、OS和PFS的独立危险因素,细胞化学染色检测MPO表达可能为评估AML疗效和预后提供一种简单而有效的手段。

Objective To analyze the percentage of myeloperoxidase (MPO)-positive acute myeloid leukemia (AML) blast cells,and to explore the correlation of MPO expression with the clinical features,gene alterations,therapeutic response and prognosis of AML.Methods The expressions of MPO in BM blasts cells of 233 newly diagnosed AML were retrospectived analyzed,they were divided into two groups using the percentage of MPO-positive blast [low (≤70%) and high (>70%)],clinical features,gene alterations,chemotherapy efficacy and prognosis were compared between the two groups.Results ①Of the 233 patients,121(51.9%) were in the low MPO group,and the rest 112(48.1%) in the high MPO group.Favorable-risk group according NCCN guidelines of AML was always MPO-high (χ^2=32.773,P<0.001),while MPO-low was closely related to poor-risk (χ^2=7.078,P=0.008);②DNMT3A mutation (χ^2=6.905,P=0.009),spliceosome genes mutation (SF3B1/SRSF2/U2AF1)(χ^2=5.246,P=0.022),RUNX1 mutation (χ^2=4.577,P=0.032),ASXL1 mutation (χ^2=7.951,P=0.005) and TP53 mutation (P=0.004) were more likely to be seen in the low MPO group,while C-KIT mutation (χ^2=8.936,P=0.003) and CEBPA mutation (χ^2=12.340,P<0.001) were more frequent in the high MPO group,especially CEBPA double mutation;③The rates of first complete remission in the low MPO group were significantly lower than that in the high MPO group (38.8% vs 68.1%,χ^2=15.197,P<0.001).Multivariate analysis showed that low MPO positivity significantly affected the CR1 unfavourably.④The overall survival (OS) and the progression-free survival (PFS) were significantly worse in the low MPO group (18.0% vs 89.4% for OS,and 11.5% vs 56.7% for PFS,P<0.001).Multivariate analysis disclosed that the low number of MPO was significantly unfavourable prognostic factor.⑤The low MPO group still showed a worse survival even when restricted to the patients with normal karyotype,the OS and the PFS were 31.1% and 18.8% respectively.Conclusions AML with different MPO expression percentage had a unique gene mutation spectrum.Low expression of MPO was an independent risk factor for CR1,OS and PFS in AML patients,which may be a simple and highly significant factor for AML patients when evaluating the therapeutic efficacy and prognosis.