title: Topoisomerase II alpha expression in acute myeloid leukaemia and its relationship to clinical outcome.
abstract: The treatment of acute myeloid leukaemia (AML) is often complicated by resistance to chemotherapeutic drugs. Many of the most effective drugs used to treat haematological malignancies target the nuclear enzyme topoisomerase II. Resistance to these drugs in vitro has been associated with quantitative and qualitative changes in the enzyme. In this study, we have investigated topoisomerase II mRNA expression in leukaemic blasts from 23 AML patients. Expression levels ranged from 1-47% relative to the haemopoietic cell line HL60 in 16 evaluable patients. Thirteen of 16 patients achieved complete remission (CR). We have therefore chosen ease of entry into CR as the most sensitive clinical correlate. Decreased topoisomerase II mRNA expression in vitro results in drug resistance. The clinical relevance of reduced expression is not known. All cases of AML and de novo AML have been studied separately. We are unable to identify a correlation between topoisomerase II mRNA levels and ease of entry into CR in either of these groups. Taking these findings into account, group size calculations have been undertaken and indicate that a multi-centre study of this question is warranted.
authors.affiliation: Department of Haematology, University of Wales College of Medicine, Heath Park, Cardiff, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: McKenna
authors.forename: R R
authors.initials: RR
authors.lastname: West
authors.forename: J A
authors.initials: JA
authors.lastname: Whittaker
authors.forename: R A
authors.initials: RA
authors.lastname: Padua
authors.forename: J A
authors.initials: JA
authors.lastname: Holmes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D012074:Remission Induction
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D012333:RNA, Messenger; D004250:DNA Topoisomerases, Type II