Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Clinical and Chemical Pathology

Glutathione S-tansfeases comprise a family of phase II detoxification enzymes involved in the metabolism of many environmental carcinogens, drugs & other xenobiotics. GSTP1 gene (I105V) mutation alters the protein function, diminishing its detoxification ability for certain mutagens and carcinogens which could result in increased DNA damage & an increased risk of leukaemogenesis. In our study we aimed to clarify the relation between GSTP1 gene (I105V) mutation and the risk of M2 & M4-AML. We also studied the relation between GSTP1 genotypes and the clinical presentations, hematological findings and treatment response in AML cases. We analyzed the presence of this mutation in 100 de novo M2 & M4-AML patients and 100 age & sex matched controls, using PCR-based restriction fragment length polymorphism (PCR-RFLP) technique. Our study suggests that individuals with at least one GSTP1 codon 105 Val allele are at a significantly high risk of developing M2 and M4 subtypes of AML. We also found a significant elevation of the valine allele among the M4 cases compared to M2 cases. GSTP1 polymorphism was associated with a higher platelet count and a lower bleeding tendency on clinical basis in M2 and M4-AML patients. Also the GSTP1 mutant genotypes were associated with more induction related mortality and less complete remission rates. Hence the present study suggests that GSTP1 Ile105Val polymorphism might influence M2 and M4-AML development, progression and response to therapy

Issued also as CD