SPRED1 Is Downregulated and a Prognostic Biomarker in Adult Acute Myeloid Leukemia
SPRED1 Is Downregulated and a Prognostic Biomarker in Adult Acute Myeloid Leukemia
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SPRED1 下调，是成人急性髓系白血病的预后生物标志物
DOI：
10.3389/fonc.2020.00204
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发表时间：
2020-02-27
影响因子：
4.7
通讯作者：
Li, Yan
中科院分区：
文献类型：
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作者：
Zhang, Rui;Zhang, Yan;Li, Yan
我们在此报告了Sprouty相关的EVH1结构域包含蛋白1(SPRED1)在成人急性髓系白血病(AML)中表达下调，是一个预后的生物标志物。我们检测了113例急性淋巴细胞白血病(AML)和22例急性淋巴细胞白血病(ALL)患者及37例健康对照骨髓单个核细胞中SPRED1mRNA的表达水平。免疫细胞化学SPRED1蛋白分析和血清SPRED1水平检测证实，AML患者的SPRED1mRNA表达水平明显低于ALL患者和健康对照组。进一步分析表明，在诱导治疗后完全缓解的大多数患者中，SPRED1的表达明显高于初诊患者。此外，SPRED1在M2和M3型中的表达显著下调。SPRED1降低的非急性早幼粒细胞白血病(Non-APL)患者的2年无进展生存率和无事件生存率显著降低。在体外，异位过表达SPRED1可导致THP-1细胞胞外信号调节蛋白激酶(ERK)磷酸化水平降低，诱导细胞凋亡，抑制细胞增殖。我们的研究结果表明，SPRED1不仅是治疗反应的预测因子，也是非APL的独立预后因素，靶向RAS-MAPK信号通路可能是治疗SPRED1下调的AML的一种有前途的策略。
We report herein that Sprouty-Related EVH1 Domain-Containing Protein1 (SPRED1) is downregulated and a prognostic biomarker in adult acute myeloid leukemia (AML). We determined mRNA levels of SPRED1 in the bone marrow mononuclear cells from adult patients, including 113 AMLs and 22 acute lymphoblastic leukemias (ALLs), as well as in 37 healthy control subjects. Significantly decreased SPRED1 mRNA expression was found in AML patients comparing to those in ALL patients and healthy controls, which was confirmed by immunocytochemistry analysis of SPRED1 protein and ELISA measurement of serum SPRED1 level. Further analysis demonstrated that SPRED1 expression was significantly higher for most patients at complete remission after induction treatment than at diagnosis. Moreover, SPRED1 expression was significantly downregulated in M2 and M3 types. Non-acute promyelocytic leukemia (non-APL) patients with decreased SPRED1 had significantly lower 2-year progression-free survival and event-free survival rates. In vitro, ectopic overexpression of SPRED1 leads to a decrease of extracellular signal-regulated kinase (ERK) phosphorylation, induction of apoptosis and reduction of proliferation of THP-1 cells. Our findings suggest SPRED1 is not only a predictor of treatment response, but also an independent prognostic factor for non-APL, and targeting Ras- Mitogen-activated protein kinase (MAPK) signaling may be a promising strategy for the treatment of AML with downregulation of SPRED1.