الفهرس 
AcknowledgementOnly 14 pages are availabe for public view
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Abstract
SUMMARY
Leukemia is defined as a group of malignant diseases in which genetic abnormalities in hematopoietic cells give rise to an unregulated clonal expansion and arrest at specific stage of normal myeloid or lymphoid hematopoiesis.
Folate metabolism plays an essential role in both DNA synthesis and methylation processes. Defects or polymorphisms in the genes of the folate dependent enzymes and deficiencies of micronutrients may influence cancer susceptibility.
5, 10-methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. Folate provides the one carbon unit required for nucleotides synthesis and for methylation of biological substances. Several polymorphisms in folate-related genes have been described. Two genetic variants in methylenetetrahydrofolatereductase (MTHFR 677 C-T and 1298A-C) have been associated with the risk of childhood acute lymphocytic leukemia.
The aim of this work was to study 5,10-Methylenetetrahydrofolate Reductase (MTHFR) gene polymorphism in children with acute lymphoblastic leukemia and to discuss its role in disease incidence and management.
This study was carried on 50 newly diagnosed patients with acute lymphoblastic leukemia(28 males, and 22 females) admitted to the Pediatric Hematology - Oncology Unit , Mansoura University children’s hospital during the period from July 2013 to July 2014 , there ages < 15 years . In addition to 52 apparently healthy children(32 males, and 20 females) with age and sex matched with the patients were involved in the study as a control group. The mean age among the cases and control groups were 5.86 and 6.17 years respectively.
All patients included in this study were subjected to careful history taking, complete physical examination and hematological investigation included: CBC bone marrow examination. In addition CSF examination for blast cells, routine biochemical investigations, chest X-ray, abdominal ultrasonography and immunophenotyping. Analysis of the MTHFR gene polymorphisms (C677T and A1298C ) was done to all studied subjects using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. These data were statistically analyzed.
In this study, immunophenotyping revealed B-ALL in 88% and non-B ALL in 12%of cases. Comparison between B-cell and T-cell leukemic cases regarding to MTHFR A1298C & C667T genotypes revealed no statistical significance (p>0.05).
There were no statistical differences in the TLC, hemoglobin concentration and platelets count between various A1298C & C677T genotypes in ALL patients. In addition, no statistical differences in the TLC, hemoglobin concentration and platelets count between various A1298C & C677T genotypes in control subjects.
As regard peripheral and marrow blasts in ALL patients at diagnosis, there were no significant differences between various C667T, A1298C genotypes,in addition to various combined C677T and A1298C genotypes.
As regard MTHFR 677C-T polymorphism, there was no detected association between the MTHFR 677C-T polymorphism and the risk of childhood ALL. Studying theMTHFR677 genotypes in both patients and control groups showed no statistically significant differences in C677T CT and TT genotypes in cases versus controls (p=0.829, OR=0.913, 95%CI= 0.399-2.088; p=1.000, OR=1.000, 95%CI= 0.281-3.563 respectively).When combining both hetero- and homozygous (CT+TT) groups; still no significant differences versus control subjects (p=0.707, OR=0.861, 95%CI= 0.394-1.882).
As regard MTHFR 1298A-C polymorphism, there was no detected association between the MTHFR 1298A-C polymorphism and the risk of childhood ALL. Studying theMTHFR 1298A-C genotypes in both patients and control groups showed no statistically significant differences in A1298C AC and CC genotypes in cases versus controls (p=0.828, OR=0.913, 95%CI=0.403-2.070; p=1.000, OR=1.000, 95%CI= 0.256-3.906 respectively).When combining both hetero- and homozygous (AC+CC) groups; no statistically significant differences was observed versus controls (p=0.852, OR=0.929, 95%CI=0.427-2.021).
Cases with CC/AA (null genotype for both C677T and A1298C) had significantly longest OS and DFS, while cases with CC/CC had significantly shortest OS and DFS.
Multivariate analysis showed that A1298C CC genotype is an independent predictor for overall and disease free survival (p=0.021, 0.023 respectively).