title: Favorable clinical outcome and unique characteristics in association with Twist1 overexpression in de novo acute myeloid leukemia.
abstract: Epithelial-mesenchymal transition (EMT) is a critical process for inducing stem-like properties of epithelial cancer cells. However, the role of EMT inducers in hematological malignancies is unknown. Twist1, an EMT inducer necessary for cell migration, has recently been found to have transcriptionally regulatory activity on the expression of Bmi1, and these two are capable of promoting tumorigenesis in a synergized manner. Knowing that Bmi1 expression is essential for maintenance of leukemic stem cells, we speculate that Twist1 might govern the pathogenesis of acute myeloid leukemia (AML) development as well. We found that upregulated Twist1 increased Bmi1 expression in AML and endued leukemic cells a higher proliferative potential and increased resistance to apoptosis. In primary AML samples, there was strong positive correlation between the expression levels of Twist1 and Bmi1. AML patients whose leukemic blasts harbored overexpressed Twist1 had a more aggressive clinical phenotype, but they were more likely to have a better clinical outcome after standard therapy. In vitro studies confirmed that Twist1-overexpressing leukemic cells were more susceptible to cytarabine, but not daunorubicin, cytotoxicity. Our findings suggest that, in a subset of AML patients, Twist1 has a prominent role in the pathogenesis of the disease that leads to unique clinical phenotypes.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.|College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: C-C
authors.initials: CC
authors.lastname: Chen
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Hematology and Oncology, Department of Medicine, Lotung Poh-Ai Hospital, Yilan, Taiwan.
authors.forename: J-Y
authors.initials: JY
authors.lastname: You
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan.|Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: J-P
authors.initials: JP
authors.lastname: Gau
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: C-E
authors.initials: CE
authors.lastname: Huang
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Chen
authors.affiliation: College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.|Division of Pulmonary and Critical Care Medicine, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Y-H
authors.initials: YH
authors.lastname: Tsai
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Chou
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: J
authors.initials: J
authors.lastname: Lung
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.|Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|Immunology Research Center, National Yang-Ming University, Taipei, Taiwan.|Genome Research Center, National Yang-Ming University, Taipei, Taiwan.
authors.forename: M-H
authors.initials: MH
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001853:Bone Marrow; D002460:Cell Line; D003561:Cytarabine / Q000627:therapeutic use; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism; D011379:Prognosis; D051879:Twist-Related Protein 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C069077:BMI1 protein, human; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D003561:Cytarabine; D063150:Polycomb Repressive Complex 1
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