Prognostic significance of beta-catenin and topoisomerase IIalpha in de novo acute myeloid leukemia.
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.
Chen
Chih-Cheng
CC
Division of Hematology Oncology, Department of Medicine, Chang Gung Memorial Hospital-Chiayi, Chiayi, Taiwan.
Gau
Jyh-Pyng
JP
You
Jie-Yu
JY
Lee
Kuan-Der
KD
Yu
Yuan-Bin
YB
Lu
Chang-Hsien
CH
Lin
Jen-Tsun
JT
Lan
Chieh
C
Lo
Wan-Hsia
WH
Liu
Jacqueline Ming
JM
Yang
Ching-Fen
CF
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*
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