Expression of glutathione transferase pi as a predictor for treatment results at different stages of acute nonlymphoblastic leukemia.
The expression of glutathione transferase pi (GST pi) was studied in leukemic cells from 60 patients with acute nonlymphoblastic leukemia at diagnosis and at progressing stages of the disease. A polyclonal rabbit antibody to human placental GST pi coupled with peroxidase antiperoxidase staining was used for immunodetection of GST pi on sections of routinely fixed bone marrow clots. All patients had received induction therapy based on an anthracycline and a standard dose of ara-C. The expression of GST pi at diagnosis was significantly correlated with response to induction therapy, duration of first remission, and overall survival. Twenty-nine of 36 samples of bone marrow from patients that entered complete remission (CR) following primary induction therapy showed a low expression, whereas nine of 16 sections from patients with resistant disease showed a high expression of GST pi (P less than or equal to 0.03). Of 40 sections that showed a low expression of GST pi, 29 (73%) were taken from patients that achieved a CR, whereas 12 of 19 sections that showed a high expression of the enzyme were from patients with resistant disease or that entered CR only after additional therapy (P less than or equal to 0.02). The median duration of first CR was 18.2 mo for patients whose cells showed a low expression of GST pi compared with 6.7 mo for those that entered CR in spite of a high expression of the enzyme (P less than or equal to 0.005). Of cells from ten patients that at the time of study were in a continuous first CR, none expressed high concentrations of GST pi. The expression of GST pi remained rather constant in most patients as the disease progressed to clinical resistance. At relapse there was no significant correlation between the expression of GST pi and treatment results but, of ten patients that entered a second CR or achieved a partial remission, only one showed a high expression of the enzyme. We conclude that there was a significant correlation between the expression of GST pi at the time of diagnosis and the subsequent treatment results and that GST pi is a useful marker for clinical resistance to cytostatic drugs in acute nonlymphoblastic leukemia.
Tidefelt
U
U
Department of Medicine, Huddinge Hospital, Sweden.
Elmhorn-Rosenborg
A
A
Paul
C
C
Hao
X Y
XY
Mannervik
B
B
Eriksson
L C
LC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D013866:Thioguanine / Q000008:administration & dosage; D013997:Time Factors
D003561:Cytarabine; D005982:Glutathione Transferase; D013866:Thioguanine; D003630:Daunorubicin