الفهرس 
CHRONIC LYMPHOCYTIC LEUKEMIAOnly 14 pages are availabe for public view
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Abstract
B-cell chronic lymphocytic leukemia is a lymphoproliferative disorder caused by the clonal expansion of B cells with a distinctive morphological appearance and surface immunophenotype. One of the most striking features of CLL is the extent of its clinical variability as some patients have an aggressive disease requiring early therapy, whereas other patients exhibit a more indolent disease with no benefit from palliative chemotherapy.
The introduction of cytogenetics and molecular technologies has enriched the study of CLL, allowing a more global assessment of the different chromosomal alterations and genetic dysregulations underlying the development of the disease and the variability of its course.
The ATM gene (11q22-23) is one of the most commonly altered gene loci in CLL and it is placed as an upstream mediator of a kinase cascade that links the detection of DNA damage to cell cycle progression, genetic recombination and apoptosis.
The p53 protein is a transcription factor that is activated by DNA damage and coordinates the cellular response to such damage by triggering apoptosis or cell-cycle arrest. It also contributes directly to the repair of some forms of DNA damage.
Critically, ATM is responsible for activating the p53, a substrate that is phosphorylated on multiple residues by ATM, both directly and indirectly, following the occurrence of DSBs. Outcomes of this activation, however, depend on the cellular context and the severity of the induced DNA damage. Indeed, p53 appears to be a crucial factor for the switch between the induction of cell cycle arrest, thus allowing DNA repair, and the induction of apoptosis which may occur in the presence of extensive or persistent DNA damage. Inactivation of P53 by mutation or deletion occurs in many human cancers and is associated with genomic instability and resistance to chemotherapy.
In light of this, the present study was conducted to study the incidence of ATM gene deletion and to detect mutant p53 expression in B-CLL patients in order to assess their prognostic impact and to correlate them with the clinical status, standard risk factors as well as patients’ outcome.
In the current work, BM/PB samples were obtained from 30 newly diagnosed B-CLL patients; 16 males and 14 females with a male to female ratio 1.1:1.0, their ages ranged from 40 to 85 years with a mean of 62.5±13.13 years. Follow up of these patients was done over a period of 6-24 months.