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脑和急性髓系白血病相关的细胞质和 ETS 相关基因的过度表达与急性髓系白血病的不良预后相关。

Over expression of brain and acute leukemia, cytoplasmic and ETS-related gene is associated with poor outcome in acute myeloid leukemia.

机构信息

Cell and Tumor Biology Group, ACTREC, Tata Memorial Centre, Navi Mumbai, India.

Homi Bhabha National Institute (HBNI), Mumbai, India.

出版信息

Hematol Oncol. 2020 Dec;38(5):808-816. doi: 10.1002/hon.2800. Epub 2020 Sep 16.

Abstract

The high expression of brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) has been reported to influence the outcome in acute myeloid leukemia (AML), but due to limited prospective studies, their role as prognostic factors is unclear. At diagnosis, the prognostic value of BAALC and ERG expression with respect to other cytogenetic and molecular markers was analyzed in 149 AML patients. Patients were divided into quartiles which resulted in the formation of four groups (G1-G4) based on expression values of BAALC and ERG and clinical response defined across groups. Groups with similar survival probabilities were merged together and categorized subsequently as high versus low expressers. Patients with high BAALC and ERG expression had significantly lower overall survival (OS; BAALC: p = 0.001 at 5 years 29.4% vs. 69.8%; ERG: p < 0.0001 at 5 years 4% vs. 50.4%) and disease-free survival (BAALC: p = 0.001 at 5 years 19.5% vs. 69.8%; ERG: p < 0.0001 at 5 years 4.2% vs. 47%). Patients were further stratified combining BAALC and ERG expression in an integrative prognostic risk score (IPRS). After a median follow-up of 54 months (95% CI 45-63 months) among survivors, IPRS for high versus low expressers was a significant predictor for OS (BAALC + ERG: 4% vs. 71.6%, p < 0.0001) and DFS (BAALC + ERG: 4.5% vs. 74.1%, p < 0.0001). In a multivariate model, IPRS of BAALC + ERG expression retained prognostic significance for OS (hazard ratio [HR] 2.96, 95%CI 1.91-4.59, p < 0.001) and DFS (HR 3.61, 95%CI 2.26-5.76, p < 0.001).

摘要

脑和急性白血病、细胞质(BAALC)和 ETS 相关基因(ERG)的高表达已被报道会影响急性髓细胞白血病(AML)的预后,但由于前瞻性研究有限,其作为预后因素的作用尚不清楚。在诊断时,分析了 149 例 AML 患者中 BAALC 和 ERG 表达相对于其他细胞遗传学和分子标志物的预后价值。根据 BAALC 和 ERG 的表达值以及跨组定义的临床反应,将患者分为四分位值,形成四个组(G1-G4)。具有相似生存概率的组被合并,并随后归类为高表达与低表达。高 BAALC 和 ERG 表达的患者总生存(OS;BAALC:p = 0.001,5 年时为 29.4% vs. 69.8%;ERG:p < 0.0001,5 年时为 4% vs. 50.4%)和无病生存(DFS;BAALC:p = 0.001,5 年时为 19.5% vs. 69.8%;ERG:p < 0.0001,5 年时为 4.2% vs. 47%)显著降低。患者在幸存者中进一步结合 BAALC 和 ERG 表达进行整合预后风险评分(IPRS)分层。在中位随访 54 个月(95%CI 45-63 个月)后,高表达与低表达者的 IPRS 是 OS(BAALC + ERG:4% vs. 71.6%,p < 0.0001)和 DFS(BAALC + ERG:4.5% vs. 74.1%,p < 0.0001)的显著预测因子。在多变量模型中,BAALC + ERG 表达的 IPRS 对 OS(危险比[HR]2.96,95%CI 1.91-4.59,p < 0.001)和 DFS(HR 3.61,95%CI 2.26-5.76,p < 0.001)具有预后意义。

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