Topoisomerase IIalpha mRNA and protein expression vs. in vitro drug resistance and clinical outcome in acute leukaemia
Uggla, B.; Tina, E.; Nahi, H.; Paul, C.; Höglund, M.; Sirsjö, A.; Tidefelt, U.
International Journal of Oncology 31(1): 153-160
2007
ISSN/ISBN: 1019-6439 PMID: 17549416 Document Number: 606073
The objective of this study was to correlate the expression of topoisomerase (topo) II alpha 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 II alpha 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 II alpha poisons and non-topo II alpha targeting drugs. Topo II alpha mRNA expression varied with relative values ranging from 0.03 to 14.20 (median 1.10). The median value for topo II alpha protein-positive cells was 23% (range 0-99%). Cell samples from patients with a high (> median value) percentage of topo II alpha-positive cells were significantly more sensitive to the topo II alpha active drugs etoposide and daunorubicin, and showed a borderline value for idarubicin (p=0.08), while there was no difference for non-topo II alpha targeting drugs. However, we did not find any significant differences in mRNA expression or the percentage of topo II alpha-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 II alpha-positive cells were compared with patients with low values. We conclude that expression of topo II alpha, determined as percentage of topo II alpha-positive cells, in leukaemic cells correlates to chemo sensitivity in vitro against topoisomerase poisons but that it does not predict clinical outcome in acute leukaemia.