الفهرس 
GLUTATHIONE-S-TRANSFERASESOnly 14 pages are availabe for public view
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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.