High expression levels of SMAD3 and SMAD7 at diagnosis predict poor prognosis in acute myeloid leukemia patients undergoing chemotherapy
High expression levels of SMAD3 and SMAD7 at diagnosis predict poor prognosis in acute myeloid leukemia patients undergoing chemotherapy
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DOI：
10.1038/s41417-018-0044-z
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发表时间：
2018-09
影响因子：
6.4
通讯作者：
Jilei Zhang;Lingxiu Zhang;Haoran Cui;Xinpei Zhang;Gaoqi Zhang;Xinrui Yang;Siyuan Yang;Zhihui Zhang;Jing Wang;K. Hu;Jinlong Shi;X. Ke;L. Fu
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文献类型：
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作者：
Jilei Zhang;Lingxiu Zhang;Haoran Cui;Xinpei Zhang;Gaoqi Zhang;Xinrui Yang;Siyuan Yang;Zhihui Zhang;Jing Wang;K. Hu;Jinlong Shi;X. Ke;L. Fu
smad1家族（SMAD1-9）通过转化生长因子-β信号通路对细胞过程的调节至关重要，并参与致癌；然而，它们在急性髓性白血病（AML）中的预后作用尚不清楚。本研究收集了84例接受化疗的新发AML患者和71例接受同种异体造血干细胞移植（alloo - hsct）的患者。Kaplan-Meier生存估计表明，在接受化疗的AML患者中，smad1 -9、smad3和smad7高表达均与较差的无事件生存期（EFS）和总生存期（OS，均p < 0.05）相关；在接受同种异体移植的患者中，高smad6表达与较短的EFS和OS相关（均p < 0.01）。多因素分析显示，只有高smad7表达对EFS和OS有独立的不良影响（P= 0.021, 0.026）。此外，highsmad3和smad7表达者的EFS和OS显著短于低表达者（P= 0.006, 0.001）。在接受同种异体造血干细胞移植的AML患者中，smad3或smad7高表达和低表达患者的EFS和OS无显著差异。我们的研究表明，smad3和smad7的高表达可预测接受化疗的AML患者的不良预后，而smad7是比ansmad3更好的预后标志物。它们对预后的影响可以通过同种异体造血干细胞移植来克服。
TheSMADfamily (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 amongSMAD1-9, highSMAD3andSMAD7expression were both associated with poor event-free survival (EFS) and overall survival (OS; allP< 0.05) in AML patients undergoing chemotherapy; and highSMAD6expression was associated with shorter EFS and OS (allP< 0.01) in patients underwent allo-HSCT. Multivariate analysis showed that only highSMAD7expression had adverse effect on EFS and OS (P= 0.021, 0.026) independently. Furthermore, HighSMAD3andSMAD7expressers 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-expressionSMAD3orSMAD7. Our study suggested that high expression ofSMAD3andSMAD7predicted adverse prognosis in AML patients undergoing chemotherapy andSMAD7was a better prognostic marker thanSMAD3. Their prognosis impact may be overcome by allo-HSCT.