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 CR(1) 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 CR(1), 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.
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（CR(1)）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CR(1)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CR(1)、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。.
Keywords: Lukemia, myeloid, acute; Mutation; Myeloperoxidase; Prognosis.