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Over-expression of FoxM1 is associated with adverse prognosis and FLT3-ITD in acute myeloid leukemia

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单位: [1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Hematol, Wuhan 430074, Peoples R China [2]Wuhan Gen Hosp Guangzhou Mil, Dept Hematol, Wuhan, Hubei, Peoples R China [3]Nanjing Univ TCM, Affiliated Hosp, Jiangsu Prov Hosp TCM, Dept Hematol, Nanjing, Jiangsu, Peoples R China
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关键词: FoxM1 Acute myeloid leukemia Prognosis AML therapy

摘要:
Forkhead box M1 (FoxM1) drives cell cycle progression and the prevention of growth arrest and is over-expressed in many human malignancies. However, the characteristics of FoxM1 in acute myeloid leukemia (AML) are not clearly understood. We investigated the expression level of FoxM1 and analyzed the correlation of FoxM1 expression with AML patient characteristics and prognoses. Changes in FoxM1 expression were detected after MV4-11 cells, which have an internal tandem duplication (ITD) of the fms-like tyrosine kinase 3 gene (FLT3-ITD), and control THP1 cells (encoding wild-type FLT3) were treated with the FLT3 receptor tyrosine kinase inhibitor AC220 (quizartinib) or FLT3 ligand (FL). Finally, we determined the apoptosis rates after the addition of the FoxM1 inhibitor thiostrepton (TST) to AML cells with or without FLT3-ITD. The expression of FoxM1 in AML patients was correlated with the presence of FLT3-ITD, genetic groups, and possibly overall survival. Inhibition of FLT3-ITD by AC220 down-regulated FoxM1 expression in MV4-11 cells, and stimulation of FLT3 by FL up-regulated FoxM1 expression in MV4-11 and THP1 cells. TST induced the apoptosis of MV4-11 and THP1 cells in a dose-dependent manner. Thus, FoxM1 is a potential prognostic marker and a promising therapeutic target in AML. (c) 2014 Elsevier Inc. All rights reserved.

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出版当年[2013]版:
大类 | 3 区 生物
小类 | 4 区 生化与分子生物学 4 区 生物物理
最新[2025]版:
大类 | 4 区 生物学
小类 | 4 区 生化与分子生物学 4 区 生物物理
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出版当年[2012]版:
Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Q3 BIOPHYSICS
最新[2023]版:
Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Q3 BIOPHYSICS

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第一作者单位: [1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Hematol, Wuhan 430074, Peoples R China [2]Wuhan Gen Hosp Guangzhou Mil, Dept Hematol, Wuhan, Hubei, Peoples R China
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