Expression of topoisomerase IIalpha in the G0/G1 cell cycle phase of fresh leukemic cells.
Topoisomerase IIalpha (topo IIalpha) is the target enzyme for several antineoplastic drugs. Correlation between low expression of topo IIalpha and drug resistance has been shown in vitro, but there is limited evidence of a correlation to initial response to treatment or to overall prognosis. Normal cells express topo IIalpha in S/G2/M phase of the cell cycle but not in G0/G1 phase. However, some data suggest that topo IIalpha could be expressed in G0/G1 phase in malignant cells. We have investigated the expression of topo IIalpha in leukemic cells from 25 patients with acute leukemia by flow cytometry, separating cells of different cell cycle phases. We demonstrated that 9/25 samples showed >50% positive cells in G0/G1, and another five samples showed >20%. This finding could possibly provide an explanation to previous difficulties in correlating topo IIalpha expression with clinical outcome. Six of eight patients, where >20% of the cells in G0/G1 were positive for topo IIalpha, entered CR, compared to one of five patients with <20% topo IIalpha positive cells in G0/G1. We suggest that topo IIalpha expression in G0/G1 in leukemic cells may be of predictive value for clinical response to cytostatic drugs.
Uggla
B
B
Department of Medicine, Orebro Medical Center Hospital, S-70185, Orebro, Sweden. bertil.uggla@orebroll.se
Möllgård
L
L
Ståhl
E
E
Mossberg
L L
LL
Karlsson
M G
MG
Paul
C
C
Tidefelt
U
U
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm; D016022:Case-Control Studies; D002453:Cell Cycle; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005434:Flow Cytometry; D016193:G1 Phase; D006801:Humans; D007938:Leukemia / Q000175:diagnosis / Q000201:enzymology / Q000473:pathology*; D008875:Middle Aged; D011379:Prognosis; D012074:Remission Induction; D016192:Resting Phase, Cell Cycle; D016896:Treatment Outcome
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D004250:DNA Topoisomerases, Type II