الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Acute myeloid leukemia is a heterogeneous clonal neoplasm characterized by accumulated genetic aberrations, which result in enhanced proliferation, block in differentiation and increased survival of the leukemic blast cells and is the most common malignant myeloid disorder in adults. It is characterized by an increase in the number of myeloid cells in the BM and an arrest in their maturation, frequently resulting in hematopoietic insufficiency with or without leukocytosis. It has an incidence of 2-3 per 100, 000 per year in children, rising to 15 per 100, 000 in older adults. It can occur at all ages but has its peak incidence in the seventh decade. Acute myeloid leukaemia accounts for approximately 25% of all leukemias in adults in the western world, and, therefore, is the most frequent form of leukemia.
Conventional methods for diagnosis of AML include peripheral blood and bone marrow examination, cytochemistry together with immunophenotyping by flowcytometry and conventional cytogenetics. Nowadays, molecular techniques are playing a major role in the diagnosis and identification of new abnormalities that may contribute to the susceptibility to AML. These molecular techniques include fluorescence insitu hybridization and polymerase chain reaction.
Cytogenetic analysis represents an important tool for both diagnosis and prognosis of AML. Among these cytogenetic data, the prognostic value of telomere shortening and telomerase activity has been suggested in various human hematopoietic malignancies.
Telomeres are repeated DNA sequences at the ends of chromosomes that are essential for chromosome protection and genomic stability. Telomerase is a ribonucleoprotein reverse transcriptase capable of compensating progressive telomere shortening. It is composed maily of two subunits: a catalytic subunit with reverse transcriptase activity (TERT), an RNA component (TERC) that acts as a template for DNA synthesis. These two subunits are encoded by two different genes located on 5p15 and 3q26 respectively, both are essential for the function of the enzyme. Telomerase is necessary for the long-term proliferation potential of human stem cells and cancer cells, and for normal tissue renewal. Ectopic expression of telomerase in normal human cells leads to extension of life-span or immortalization of many cell types.
In most cancers including AML, telomerase is expressed at levels that are substantially higher than in normal cells. A known consequence of telomerase up regulation (which is considered to play a critical role in oncogenesis) is maintenance of telomere length, and thus evasion by cancer cells of apoptosis that are associated with the steady decrease in telomere length in normal cells.
The aim of this study was to estimate human telomerase reverse transcriptase (hTERT) and human telomerase RNA component (hTERC) genes’ copy number in adult AML patients using fluorescence in situ hybridization (FISH) and to correlate this with other clinical and laboratory parameters.
This study was carried out on 25 adult patients (18-60 yrs) newly diagnosed with AML. All patients were subjected to full history taking, complete clinical examination and investigations. The investigations included CBC, bone marrow aspiration,