title: Prognostic significance of beta-catenin and topoisomerase IIalpha in de novo acute myeloid leukemia.
abstract: The Wnt/beta-catenin signaling is important for controlling self-renewal of hematopoietic stem cells and its constitutive activation has recently been documented in a significant proportion of acute myeloid leukemia (AML) cases. Topoisomerase IIalpha (Topo IIalpha) is a marker of cell proliferation and a crucial target for anthracycline cytotoxicity, the mainstay of management employed in AML. We retrospectively investigated the prognostic roles of beta-catenin and topo IIalpha in a cohort of 59 patients with newly diagnosed AML by immunohistochemistry. Aberrant beta-catenin expression was demonstrated in 13 patients (22%), and it was more likely to occur in those with unfavorable karyotypes. Advanced age and poor performance status adversely influenced the achievement of complete remission, while neither aberrant beta-catenin expression nor enhanced topo IIalpha activity did. On multivariate survival analysis, four factors independently predicted a shortened overall survival: aberrant beta-catenin expression, high topo IIalpha activity, poor-risk cytogenetics, and presence of at least one comorbidity factor. Our results suggest that both beta-catenin and topo IIalpha independently predicted an adverse prognosis and might serve as new markers for risk stratification in AML patients.
authors.affiliation: Division of Hematology Oncology, Department of Medicine, Chang Gung Memorial Hospital-Chiayi, Chiayi, Taiwan.
authors.forename: Chih-Cheng
authors.initials: CC
authors.lastname: Chen
authors.forename: Jyh-Pyng
authors.initials: JP
authors.lastname: Gau
authors.forename: Jie-Yu
authors.initials: JY
authors.lastname: You
authors.forename: Kuan-Der
authors.initials: KD
authors.lastname: Lee
authors.forename: Yuan-Bin
authors.initials: YB
authors.lastname: Yu
authors.forename: Chang-Hsien
authors.initials: CH
authors.lastname: Lu
authors.forename: Jen-Tsun
authors.initials: JT
authors.lastname: Lin
authors.forename: Chieh
authors.initials: C
authors.lastname: Lan
authors.forename: Wan-Hsia
authors.initials: WH
authors.lastname: Lo
authors.forename: Jacqueline Ming
authors.initials: JM
authors.lastname: Liu
authors.forename: Ching-Fen
authors.initials: CF
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000032:analysis*; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D015331:Cohort Studies; D015897:Comorbidity; D003561:Cytarabine / Q000627:therapeutic use; D004250:DNA Topoisomerases, Type II / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D051153:Wnt Proteins / Q000502:physiology; D051176:beta Catenin / Q000032:analysis*
chemical_list: D000951:Antigens, Neoplasm; D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D003561:Cytarabine; D004250:DNA Topoisomerases, Type II