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Abstract Glutatione-S-transferases (GSTs) are xenobiotic metabolizing enzymes contributing to the detoxification of activating carcinogens as environmental pollutants, benzopyrenes and other polyaromatic hydrocarbons. Inherited differences in the capacity of these enzymes might be an important genetic factor leading to susceptibility to cancer . Glutathione-S-transeferases (GSTs) have been implicated as susceptibility genes in this context for a number of cancers including hematological malignancies like AML – CML . Individuals carrying less efficient alleles of detoxifying genes, vary in their ability to metabolize carcinogens and hence to detoxify chemicals, leading to different risk in getting cancer .. Myloid leukaemias are heterogenous diseases which are subdivided into acute and chronic myeloid leukaeimas. Acute myeloid leukaemia is neoplastic proliferation in haematopoietic precursor cells, resulting in overgrowth of myeloblast and other immature myeloid cells. The malignant cells replace the bone marrow, circulate in the blood and may accumulate in other tissues. Acute myeloid leukaemia (AML) in adults has a 20% 5-years disease-free survival, despite treatment with aggressive cytotoxic chemotherapy. For several decades AML has been characterized on the basis of morphology, special stain, cytogenetics, and cell surface markers. However, recent studies on molecular characterization of specific defects in acute leukaemias have provided new avenues for targeted therapy . Chronic myeloid leukaemia is a malignancy of the haematopoietic stem cell, Characterized by the presence of Philadelphia chromosome and/or BCR-ABL fusion gene. DNA damage in the haematopoietic precursor cell is the essential prerequisite for the development of leukaemia and the body has developed a series of mechanisms aimed at preventing such damage Reciprocal translocation between chromosome 9 and 22 leads to juxta-position of BCR-ABL gene. The resultant increased tyrosine kinase activity is responsible for the initiation and maintenance of leukaemic process. The events responsible for the genesis of Philadelphia chromosome are not well known; only causative factor to be associated with CML is exposure to radioactivity. It is known that environmental exposure to cytotoxic and genotoxic agents particularly derived from benzene may be associated with increased risk of CML . In this study, we aimed to define GSTT1 & GSTM1 genotypes in de-novo cases of (acute & chronic) myeloid leukaemias through a multiplex PCR technique and correlate this expression with the laboratory data and clinical outcome following induction chemotherapy. This study was carried out on 50 cases of newly diagnosed cases of myeloid leukaemias: 25 cases diagnosed as AML, 12 male and 13 female. Their age ranged between 15 and 61 years, SD ±13.8. And 25 cases diagnosed as CML, 10 male and 15 female. Their age ranged between 17 and 73 years, SD ±14.6 and 30 geographically and racially matched healthy controls, 13 male and 17 female. The study revealed increased risk of acute myeloid leukaemia with null genotype GSTT1, with risk 7.04 folds and was associated with poor prognosis, and increased risk of chronic myeloid leukaemia with null genotype GSTT1, with risk 4.3 folds and was associated with poor prognosis. Genotyping of these xenobiotic enzymes may be of value to modify the drug doses of chemotherapy and for the prognosis of myeloid leukaemias. from our study we can conclude that the null GSTT1 genotype could be associated with increased risk of acute and chronic myeloid leukaemia. GSTT1 null genotype was apparently related to response, drug side effect and prognosis of patients with acute myeloid leukaemia. GSTT1 and GSTM1 genotypes might be useful in selecting appropriate chemotherapy regimen for patients with acute leukaemia Key word: GSTT1: Glutathione-S-Transferase Theta 1. GSTM1: Glutathione-S-Transferase Mu 1. |