الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. It is a neoplasm of immature lymphoid progenitors which originate from various important genetic lesions including mutations that impart the capacity for unlimited self-renewal and stage-specific developmental arrest. Ionizing radiation has been significantly linked to childhood leukemia.
The x-ray repair cross complementing group 1 (XRCC1) gene, a protein coding gene, is an important component of various DNA repair pathways specially base excision repair (BER); contributing to DNA-damage processing and genetic stability. Cells deficient in XRCC1 are hypersensitive to DNA damaging agents such as ionizing radiation and alkylating agents. Thus, altered BER efficiency caused by XRCC1 polymorphisms can potentially have a big impact on cancer risk.
5-hydroxymethyl cytosine (5-hmC) is a novel promising epigenetic marker which is involved in regulating the balance between pluripotency and differentiation that is often disrupted in hematopoietic malignancies. In addition, 5-hmC is thought to be a critical step on the pathway to DNA repair driven DNA demethylation. BER pathway is considered to be a likely mechanism for this pathway. Thus, theoretically there may be a relation between XRCC1 as an important BER protein and 5-hmC level.
The aim of the present work was to assess the role of gene polymorphism of the repair enzyme XRCC1 as a genetic modification and 5-hydroxymethylated DNA as epigenetic modification in pathogenesis of acute lymphoblastic leukemia in Egyptian children and to evaluate their potential roles in predicting therapeutic outcomes to induction chemotherapy of those patients.
In order to achieve these goals, this study included 50 newly diagnosed ALL patients and 30 age and sex matched healthy children. Following proper selection of patients and control subjects, the following laboratory tests were performed:
1- PCR to detect the XRCC1 Arg194Trp polymorphism.
2- PCR to detect the XRCC1 Arg399Gln polymorphism.
3- Colorimetric determination of global DNA hydroxymethylation by measuring levels of 5-hmC in blood.
After induction chemotherapy, patients were reevaluated to assess the initial response to therapy as regards bone marrow aspirate after 14 and 28 days of treatment to determine remission status in response to induction chemotherapy.