Glutathione S-transferase genotypes in children who develop treatment-related acute myeloid malignancies. Leukemia 2000 Feb;14(2):232-7
Date
02/16/2000Pubmed ID
10673738DOI
10.1038/sj.leu.2401660Scopus ID
2-s2.0-0033954510 (requires institutional sign-in at Scopus site) 65 CitationsAbstract
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.
Author List
Woo MH, Shuster JJ, Chen C, Bash RO, Behm FG, Camitta B, Felix CA, Kamen BA, Pui CH, Raimondi SC, Winick NJ, Amylon MD, Relling MVMESH terms used to index this publication - Major topics in bold
Antineoplastic Agents, PhytogenicChild
Child, Preschool
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System
Female
Genotype
Glutathione Transferase
Humans
Leukemia, Myeloid, Acute
Male
Mixed Function Oxygenases
Neoplasms, Second Primary
Podophyllotoxin
Polymerase Chain Reaction
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Risk Factors
United States
