الفهرس 
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Abstract
Summary
Leukemia is a group of cancers that usually begin in the bone marrow and result in high numbers of abnormal white blood cells. These white blood cells are not fully developed and are called blasts or leukemia cells. Symptoms may include bleeding and bruising problems, feeling tired, fever, and an increased risk of infections. These symptoms occur due to a lack of normal blood cells.
EIF4E is a eukaryotic translation initiation factor involved in directing ribosomes to the cap structure of mRNAs. It is a 24-kD polypeptide that exists as both a free form and as part of a multiprotein complex termed EIF4F. The EIF4E polypeptide is the rate-limiting component of the eukaryotic translation apparatus and is involved in the mRNA-ribosome binding step of eukaryotic protein synthesis. The other subunits of EIF4F are a 50-kD polypeptide, termed EIF4A, that possesses ATPase and RNA helicase activities, and a 220-kD polypeptide, EIF4G.
The eukaryotic translation initiation factor (EIF4E) is a potent oncogene. In fact, its overexpression in human cancer often correlates with poor prognosis.
EIF4E is ubiquitously expressed, and its presence is essential for viability of cells or whole organisms. The level of expression and phosphorylation status may vary between tissues and cellular differentiation state. It was shown that EIF4E is over-expressed in many types of cancer.
EIF4E is localized both in the cytoplasm and the nucleus of the cell. Up to 68% of EIF4E is found in the nucleus of cells from a wide variety of species ranging from yeast to humans. Localization of EIF4E can also be dynamic.
The multistep process by which ribosomes are recruited to mature mRNA sequences is a highly regulated process that requires the coordination of free 40S ribosomal subunits, mRNA, and the eukaryotic translation initiator factor 4F (EIF4F) translation initiation complex.
The EIF4E protein provides the critical interface between mRNA, recruitment of EIF4A and EIF4G, and the 40S ribosomal subunit because it binds to the 7-methyl guanosine cap structure at the end of mRNAs.
EIF4E can modulate gene expression at two levels: by exporting mRNAs to the cytoplasm increasing their concentration and by enhancing the translational efficiency of transcripts that are already in the cytoplasm. Not all transcripts are affected at both levels. Importantly, EIF4E requires its m7G cap binding function in order to act in either of these functions.
EIF4E overexpression has been demonstrated in human tumors of the breast, head and neck, colon, prostate, bladder, cervix and lung, and has been related to disease progression. Overexpression of EIF4E in experimental models dramatically alters cellular morphology, enhances proliferation and induces cellular transformation, tumorigenesis and metastasis. Conversely, blocking EIF4E function by expression of antisense RNA, or overexpression of the inhibitory EIF4E binding proteins (4E-BPs), suppresses cellular transformation, tumor growth, tumor invasiveness and metastasis.
The current study was conducted on 88 leukemic patients who were diagnosed as 44 acute leukemia patients (33 AML and 31 ALL) and 24 CML patients.
Twenty normal healthy volunteers age and sex matched served as a control group.
They were 52 male patients (21 AML&18 ALL& 13CML) and 36 female patients (12 AML &13 ALL&11CML), while controls were 9 males and 11 females.
All the Patients were subjected to the following:
Thorough History Taking.
Thorough Clinical Examination.
Routine Laboratory Investigations:
Complete Blood Count (CBC)
Bone Marrow Examination
Cytochemical Stain Studies
Immunophenotyping Analysis
Specific Laboratory Investigations: Study of the EIF4E mRNA in peripheral blood mononuclear cells (PBMNCS) using RT-PCR.
There was statistically significant difference between EiF4E expression level in AML/Control (p=0.002), ALL/Controls (p=0.029), CML/Control (p=0.001).
Comparing the 3 groups as regards the EiF4E gene level there was no statistical significant difference (p=0.148).
While there was no statistically significant differences(p>0.05) in the EiF4E expression levels as regards clinical and laboratory findings, i.e., gender, BM infiltration, presence of hepatomegaly, splenomegaly and lymphadenopathy, phasaes of CML (chronic,accelerated and blastic).
There was no significant correlation between AML group and EiF4E gene level as regards age, TLC, hemoglobin and platelets (p>0.05), while there was significant positive correlation on comparing bone marrow blast% and EiF4E gene level (r=0.545and p=0.001).
There was no significant correlation between ALL group and EiF4E gene level as regards age, TLC, hemoglobin, platelets and bone marrow blasts% (p>0.05).
There was no significant correlation between CML group and EiF4E gene level as regards age, TLC, hemoglobin, platelets peripheral blood blasts% and LAP score (p>0.05).
We conclude that the human tumor related gene EiF4E expression in leukemia primary cells significantly increase, which may play an important role in growth process of leukemia cells.
Also the results showed that this procedure was highly discriminating between healthy subjects and ALL,AML and CML patients and strongly support the idea that a valuable diagnostic test for cancer might be developed using this genetic marker in plasma.