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Topoisomerase IIα mRNA and protein expression vs. in vitro drug resistance and clinical outcome in acute leukaemia
Department of Medicine, Örebro University Hospital, Örebro.
Clinical Research Centre, Örebro University Hospital, Örebro.
Department of Clinical Hematology, Karolinska University Hospital, Huddinge, Stockholm; Karolinska Institute, Stockholm.
Department of Clinical Hematology, Karolinska University Hospital, Huddinge, Stockholm; Karolinska Institute, Stockholm.
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2007 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 31, no 1, 153-160 p.Article in journal (Refereed) Published
Abstract [en]

The objective of this study was to correlate the expression of topoisomerase (topo) IIalpha to in vitro drug sensitivity and to the clinical outcome in patients with acute leukaemia. Leukaemic cells were isolated from bone marrow or blood from 94 patients. Topo IIalpha mRNA (n=58) and protein (n=60) expression was determined by real-time RT-PCR and flow cytometry, respectively. In both groups, chemosensitivity testing by a bioluminescence ATP assay was performed to a variable extent for both topo IIalpha poisons and non-topo IIalpha targeting drugs. Topo IIalpha mRNA expression varied with relative values ranging from 0.03 to 14.20 (median 1.10). The median value for topo IIalpha protein-positive cells was 23% (range 0-99%). Cell samples from patients with a high (>median value) percentage of topo IIalpha-positive cells were significantly more sensitive to the topo IIalpha active drugs etoposide and daunorubicin, and showed a borderline value for idarubicin (p=0.08), while there was no difference for non-topo IIalpha targeting drugs. However, we did not find any significant differences in mRNA expression or the percentage of topo IIalpha-positive cells in patients who achieved complete remission after at most two induction courses compared with those who did not, nor did we find any difference in survival when patients with high mRNA expression/percentage of topo IIalpha-positive cells were compared with patients with low values. We conclude that expression of topo IIalpha, determined as percentage of topo IIalpha-positive cells, in leukaemic cells correlates to chemosensitivity in vitro against topoisomerase poisons but that it does not predict clinical outcome in acute leukaemia.

Place, publisher, year, edition, pages
Athens: Editorial Academy of the International Journal of Oncology , 2007. Vol. 31, no 1, 153-160 p.
Keyword [en]
topoisomerase IIa, acute leukaemia, drug resistance, prognosis, reverse transcriptase-polymerase chain reaction, flow cytometry
National Category
Medical and Health Sciences Cancer and Oncology
Research subject
Medicine; Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-10516PubMedID: 17549416Scopus ID: 2-s2.0-34548571944OAI: oai:DiVA.org:oru-10516DiVA: diva2:313642
Available from: 2010-04-27 Created: 2010-04-27 Last updated: 2015-04-01Bibliographically approved
In thesis
1. Biological markers in breast cancer and acute leukaemia with focus on drug resistance
Open this publication in new window or tab >>Biological markers in breast cancer and acute leukaemia with focus on drug resistance
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2010. 68 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 43
Keyword
Breast cancer, acute leukaemia, drug resistance, toposiomerase IIa, BCRP, HER2, SLC25A43, flow cytometry, real time PCR, whole genome screening
National Category
Medical and Health Sciences Cancer and Oncology
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-10519 (URN)978-91-7668-724-6 (ISBN)
Public defence
2010-05-21, Bohmanssonsalen, Universitetssjukhuset, Örebro, 13:00 (Swedish)
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Available from: 2010-04-27 Created: 2010-04-27 Last updated: 2011-04-26Bibliographically approved

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