title: Over-expression of FoxM1 is associated with adverse prognosis and FLT3-ITD in acute myeloid leukemia.
abstract: 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.
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Hematology, Wuhan General Hospital of Guangzhou Military, Wuhan, Hubei, China.
authors.forename: Long-long
authors.initials: LL
authors.lastname: Liu
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: zdh62@aliyun.com.
authors.forename: Dong-hua
authors.initials: DH
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Mao
authors.affiliation: Department of Hematology, Wuhan General Hospital of Guangzhou Military, Wuhan, Hubei, China.
authors.forename: Xin-hua
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of TCM, Nanjing, Jiangsu, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D052160:Benzothiazoles / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D010671:Phenylurea Compounds / Q000494:pharmacology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020080:Tandem Repeat Sequences; D013883:Thiostrepton / Q000494:pharmacology; D015854:Up-Regulation; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D052160:Benzothiazoles; D014408:Biomarkers, Tumor; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D010671:Phenylurea Compounds; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C544967:quizartinib; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; D013883:Thiostrepton
keywords: AML therapy; Acute myeloid leukemia; FoxM1; Prognosis