title: High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome for standard chemotherapy in acute myeloid leukaemia.
abstract: BACKGROUND
  Cytosine arabinoside-based chemotherapy coupled with anthracycline is currently the first-line treatment for acute myeloid leukaemia (AML), but diverse responses to the regimen constitute obstacles to successful treatment. Therefore, outcome prediction to chemotherapy at diagnosis is believed to be a critical consideration.
  
  
  METHODS
  The mRNA expression of 12 genes closely involved in the actions of cytosine arabinoside and anthracycline was evaluated by real-time reverse transcriptase PCR (RT-PCR), in 54 diagnostic bone marrow specimens of M2-subtype AML.
  
  
  RESULTS
  Low expression levels of ribonucleotide reductase M2 (RRM2) and high expression levels of topoisomerase 2 beta (TOP2B) were correlated with longer survival in a univariate analysis. Another interesting finding is that high ratios of TOP2B/RRM2 and TOP2B/TOP2 alpha (TOP2A) in a combined analysis were also shown to have a prognostic impact for longer survival with improved accuracy. Among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the TOP2B/TOP2A ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (HR, 0.24; P=0.002) and overall survival (HR, 0.29; P=0.005).
  
  
  CONCLUSIONS
  Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype.
authors.affiliation: Division of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Song
authors.forename: S H
authors.initials: SH
authors.lastname: Kweon
authors.forename: H-J
authors.initials: HJ
authors.lastname: Kim
authors.forename: T-H
authors.initials: TH
authors.lastname: Lee
authors.forename: W-S
authors.initials: WS
authors.lastname: Min
authors.forename: H-J
authors.initials: HJ
authors.lastname: Kim
authors.forename: Y-K
authors.initials: YK
authors.lastname: Kim
authors.forename: S Y
authors.initials: SY
authors.lastname: Hwang
authors.forename: T S
authors.initials: TS
authors.lastname: Kim
mesh_terms: D018943:Anthracyclines / Q000008:administration & dosage; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D001853:Bone Marrow / Q000378:metabolism; D045744:Cell Line, Tumor; D003561:Cytarabine / Q000008:administration & dosage; D004250:DNA Topoisomerases, Type II / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D012262:Ribonucleoside Diphosphate Reductase / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D003561:Cytarabine; C093713:ribonucleotide reductase M2; D012262:Ribonucleoside Diphosphate Reductase; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human; C000618814:TOP2B protein, human