Glutathione S-transferases Null Genotype in Acute Myeloid Leukaemia

Document Type: Original Article

Authors

1 Genetic Department, Clinical and Research Center for Infertility, Shahid Sadughi University of Medical Sciences, Yazd, Iran

2 MRD Lab, King’s College, London, UK.

3 Department of Haematology, Manchester Royal Infirmary, Manchester, UK.

Abstract

Background: The glutathione S-transferase (GST) family of metabolising enzymes plays an important role in the detoxification of mutagens and carcinogens. The expression of many of these cancer susceptibility enzymes is genetically polymorphic. An increased frequency of GST-null genotypes has been associated with several malignancies.
Objective: To investigate the rate of GSTT1 and GSTM1 null genotypes in AML patients and to determine its importance in prognosis of the disease.
Methods: DNA was extracted by phenol/chloroform method from peripheral blood or bone marrow of 180 white Caucasian patients. A multiplex PCR method was used simultaneously to amplify regions of GSTM1, GSTT1, and b-globin genes in genomic DNA. The survival curves were analyzed by the Kaplan-Meier method and compared by the log-rank test (Mantel-Cox) using the SPSS software program.
Results: Of the total of 180 patients, 23 cases (12.8%) showed null genotypes in both genes, while in 52 patients (28.9%) both genes were wild-types. GSTM1 null-GSTT1 wild-type was detected in 91 patients (50.6%) and GSTM1 wild-type-GSTT1 null genotype was detected in 14 patients (7.8%). These rates are within the upper limit of the rates detected in the normal European population. There was no significant difference in the overall survival and in disease free survival between different groups.
Conclusion: These observations suggest that the inherited absence of the GSTT1 and GSTM1 carcinogen detoxification pathway may be related to carcinogenesis but it is not an important determinant of prognosis in AML.

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