Frequency of Genetic Deletions of the Glutathione-S Transferase (Gst) Gene in Mexican Patients with De Novo Acute Leukemia: A Preliminary Report from the “Instituto Tecnologico De Monterrey-Hematology Research Group”.

Although there have been extraordinary advances in leukemia therapy, there is still a large subset of cases in which complete remission or prolonged leukemia-free survival cannot be achieved. Some of this variability in results is thought to be related to the differences in the effect of chemotherapy drugs on different patients. In many cases, these differences may be associated with the presence of genetic alterations that produce defective drug-metabolizing enzymes, drug transporters or drug targets. One of these is the glutathione-S transferase (GST) gene, which is known to catalyze the conjugation of toxic compounds, such as aliphatic aromatic heterocyclic radicals and epoxides, among others, to glutathione. The enzymes encoded by this gene detoxify polycyclic aromatic hydrocarbons and conjugated isothiocyanates.

Objective: Our aim is to evaluate the frequency of deletions in GSTT1 and GSTM1 of the GST gene in Mexican patients with de novo acute leukemia.

Methods: Starting in July 2003 and up until now, have included 75 samples from as many patients diagnosed with de novo acute leukemia, regardless of age, sex, or leukemia type. After obtaining informed consent, we drew blood, purified DNA and performed PCR to look for deletions in the GST gene (variants GSTT1 and GSTM1).

Results: We found GSTM1 positiveness in 54 samples (72%), of those, 24 (44.5%) were ALL and 30 (55.5%) AML. We had 18 samples (24%) positive for the GSTT1 deletion; of those, 10 (55.5%) were from patients with ALL and 8 (44.4%) from AML patients.

Conclusions; As far as we can tell this is the first report of the frequency of these genetic deletions in Mexican acute leukemia patients. Recently a Mexican group studying the possible association of GSTT1 to lung cancer found that among Mexican controls, the frequency of this deletion was around 4.5%. This result would appear to indicate, as has been done by some other authors, that regardless of the possibility of becoming a prognostic factor, at least some polymorphism of the GST gene could be related to the genesis of this disease.