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Lookup NU author(s): Dr Linda Hogarth,
Dr Michael Reid,
Professor Stephen Proctor,
Dr Peter Hamilton,
Dr Andrew Hall
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Lymphoblasts were separated from the peripheral blood or bone marrow of 19 children (age 1-15, median 4 years) and 13 adults (age 18-59, median 47 years) with acute lymphoblastic leukaemia (ALL). Twenty-one samples were examined at presentation (16 from children and five from adults) and 13 at relapse (three children and ten adults). Glutathione (GSH) levels in leukaemic blasts were compared with in vitro sensitivity to a variety of cytotoxic drugs assessed using 3-(4-5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) as an indicator of cell viability. There was a statistically significant positive correlation between GSH levels and in vitro sensitivity to daunorubicin (Spearman's rank correlation coefficient r(s) = 0.38, p < 0.04), melphalan (r(s) = 0.39, p < 0.04) and prednisolone (r(s) = 0.48, p < 0.01), but not mitozantrone, etoposide or 6-thio-guanine. There was no statistically significant difference in median GSH levels between blasts from children and adults or between samples taken at presentation or relapse. The sample median GSH levels in blasts from patients who responded to therapy (n = 21) and those who did not (n = 7) were 1.05 fmol/cell (97.3% confidence interval (CI) 0.78-1.52) and 2.66 fmol/cell (98.4% CI 0.53-5) respectively, and this difference was statistically significant (p < 0.02, Mann-Whitney U test). In two patients for whom paired samples were available, GSH levels in blasts on relapse were greater than 2-fold higher than on presentation. These results provide evidence that elevations of GSH in leukaemic blasts may be associated with resistance to drugs used in the treatment of children and adults with ALL.
Author(s): Maung, Z. T., Hogarth, L. A., Reid, M. M., Proctor, S. J., Hamilton, P. J., Hall, A. G.
Publication type: Article
Publication status: Published
Print publication date: 01/09/1994
ISSN (print): 0887-6924
ISSN (electronic): 1476-5551
PubMed id: 8090028