Glutathione S-transferase genotypes in children who develop treatment-related acute myeloid malignancies

M. H. Woo, J. J. Shuster, C. Chen, R. O. Bash, F. G. Behm, B. Camitta, C. A. Felix, B. A. Kamen, C. H. Pui, S. C. Raimondi, N. J. Winick, M. D. Amylon, M. V. Relling

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

Epipodophyllotoxin-associated secondary myeloid leukemia is a devastating complication of acute lymphoblastic leukemia (ALL) therapy. The risk factors for treatment-related myeloid leukemia remain incompletely defined. Genetic deficiencies in glutathione S-transferase (GST) activities have been linked to higher frequencies of a number of human malignancies. Our objective was to determine whether the null genotype for GSTM1, GSTT1, or both, was more frequent in children with ALL who developed treatment-related myeloid malignancies as compared to those who did not. A PCR technique was used to assay for the null genotype for GSTM1 and GSTT1 in 302 children with ALL, 57 of whom also subsequently developed treatment-related acute myeloid leukemia or myelodysplastic syndrome. Among children with ALL who did not develop treatment-related myeloid malignancies, the frequencies of GSTM1 and GSTT1 wild-type, GSTM1 null-GSTT1 wild-type, GSTM1 wild type-GSTT1 null, and GSTM1 and GSTT1 null genotypes were 40%, 42%, 9% and 9%, respectively. The corresponding frequencies for patients who developed acute myeloid malignancies were 42%, 32%, 11% and 16%, respectively (P = 0.26). A statistically significant increase in the frequency of the GST null genotype was observed in male patients who developed myeloid malignancies as compared to male ALL control patients (P = 0.036), but was not observed in female patients (P = 0.51). Moreover, a logistic regression analysis of possible predictors for myeloid malignancies, controlling for gender and race, did not reveal an association of GSTM1 or GSTT1 null genotypes (P = 0.62 and 0.11, respectively) with treatment-related malignancies. Our data suggest that GSTM1 and GSTT1 null genotypes may not predispose to epipodophyllotoxin-associated myeloid malignancies.

Original languageEnglish (US)
Pages (from-to)232-237
Number of pages6
JournalLeukemia
Volume14
Issue number2
DOIs
StatePublished - Jan 1 2000

Keywords

  • Acute myeloid leukemia
  • Epipodophyllotoxins
  • GSTM1
  • GSTT1
  • Glutathione S-transferase genotype

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Woo, M. H., Shuster, J. J., Chen, C., Bash, R. O., Behm, F. G., Camitta, B., Felix, C. A., Kamen, B. A., Pui, C. H., Raimondi, S. C., Winick, N. J., Amylon, M. D., & Relling, M. V. (2000). Glutathione S-transferase genotypes in children who develop treatment-related acute myeloid malignancies. Leukemia, 14(2), 232-237. https://doi.org/10.1038/sj.leu.2401660