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在接受化疗的急性髓系白血病患者中,诊断时高表达的 SMAD3 和 SMAD7 预示着预后不良。

High expression levels of SMAD3 and SMAD7 at diagnosis predict poor prognosis in acute myeloid leukemia patients undergoing chemotherapy.

机构信息

Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, 100191, China.

Department of Hematology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 7453100, China.

出版信息

Cancer Gene Ther. 2019 May;26(5-6):119-127. doi: 10.1038/s41417-018-0044-z. Epub 2018 Sep 4.

Abstract

The SMAD family (SMAD1-9) was critically important for regulating cellular process through transforming growth factor-β signaling pathway, and contributed to carcinogenesis; however, their prognostic roles in acute myeloid leukemia (AML) remained unclear. This study collected 84 de novo AML patients treated with chemotherapy and 71 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Kaplan-Meier survival estimate indicated that among SMAD1-9, high SMAD3 and SMAD7 expression were both associated with poor event-free survival (EFS) and overall survival (OS; all P < 0.05) in AML patients undergoing chemotherapy; and high SMAD6 expression was associated with shorter EFS and OS (all P < 0.01) in patients underwent allo-HSCT. Multivariate analysis showed that only high SMAD7 expression had adverse effect on EFS and OS (P = 0.021, 0.026) independently. Furthermore, High SMAD3 and SMAD7 expressers had significantly shorter EFS and OS than low expressers (P = 0.006, 0.001). In AML patients who went through allo-HSCT, there were no significant differences for EFS and OS between patients with high and low-expression SMAD3 or SMAD7. Our study suggested that high expression of SMAD3 and SMAD7 predicted adverse prognosis in AML patients undergoing chemotherapy and SMAD7 was a better prognostic marker than SMAD3. Their prognosis impact may be overcome by allo-HSCT.

摘要

SMAD 家族(SMAD1-9)在转化生长因子-β信号通路中对调节细胞过程至关重要,并有助于癌症发生;然而,它们在急性髓系白血病(AML)中的预后作用仍不清楚。本研究收集了 84 例接受化疗的初治 AML 患者和 71 例接受异基因造血干细胞移植(allo-HSCT)的患者。Kaplan-Meier 生存估计表明,在接受化疗的 AML 患者中,SMAD1-9 中高表达 SMAD3 和 SMAD7 均与无事件生存(EFS)和总生存(OS)不良相关(均 P<0.05);高表达 SMAD6 与 EFS 和 OS 较短相关(均 P<0.01)allo-HSCT 患者。多变量分析表明,只有高表达 SMAD7 对 EFS 和 OS 有不良影响(P=0.021,0.026)。此外,SMAD3 和 SMAD7 高表达者的 EFS 和 OS 明显短于低表达者(P=0.006,0.001)。在接受 allo-HSCT 的 AML 患者中,EFS 和 OS 在 SMAD3 或 SMAD7 高表达和低表达患者之间无显著差异。我们的研究表明,SMAD3 和 SMAD7 的高表达预示着接受化疗的 AML 患者预后不良,SMAD7 是比 SMAD3 更好的预后标志物。allo-HSCT 可能会克服它们的预后影响。

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