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. 2001 Jan;54(1):31–36. doi: 10.1136/jcp.54.1.31

Topoisomerase IIα and IIß expression in childhood acute lymphoblastic leukaemia: relation to prognostic factors and clinical outcome

A Lodge 1, A Hall 1, M Reid 1, G McIntosh 1, M Steward 1, J Anderson 1, C Horne 1, B Angus 1
PMCID: PMC1731267  PMID: 11271785

Abstract

Background/Aims—Many regimens used in the treatment of childhood acute lymphoblastic leukaemia (ALL) include Daunorubicin or Etoposide, which act as topoisomerase poisons. It has been suggested that there may be a relation between topoisomerase expression and response to topoisomerase poisons, based mainly on results from in vitro studies. Therefore, the aim of this study was to investigate this relation in a clinical setting and determine whether topoisomerase IIα and IIß might be of predictive value in ALL.

Methods—Cellular expression of topoisomerases IIα and IIß was assessed in 177 cases of ALL by immunohistochemistry using monoclonal antibodies to the two enzymes. The percentages of cell nuclei showing positive staining for topoisomerase IIα and IIß expression were assessed.

Results—Taking the series as a whole, a clear separation of survival curves was seen with the established prognostic markers white blood cell (WBC) count, CD10 status, and sex. However, topoisomerase IIα and IIß expression showed no relation to survival. No association was found between the topoisomerases and the prognostic markers CD10 and WBC count; however, topoisomerase IIα expression was found to be related to sex, with expression being lower in girls (p = 0.002).

Conclusions—These results suggest that the response to topoisomerase poisons cannot be predicted by the assessment of topoisomerase IIα and IIß expression as defined by immunohistochemistry.

Key Words: topoisomerase • leukaemia • prognosis • immunohistochemistry

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Figure 1 Western blot showing immunoreactivity of TOPO2ß-8.71 with a 180 kDa protein (left) and NCL-TOPOIIA with a 170 kDa protein (right) using a lysate of a RAJI cell line.

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Figure 2 Immunohistochemical staining of (A) topoisomerase IIα and (B) topoisomerase IIß in an acute lymphoblastic leukaemia bone marrow trephine showing extensive infiltration. Note intensive staining of tumour cell nuclei in both instances.

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Figure 3 Kaplain Meier survival analysis for all patients (n = 160) according to (A) presenting white blood cell (WBC) count, (B) CD10, (C) sex, (D) age, (E) topoisomerase IIα, and (F) topoisomerase IIß.

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