الفهرس 
Chapter i introduction & aim of the workOnly 14 pages are availabe for public view
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Abstract
B-chronic lymphocytic leukemia (B-CLL) is a malignant lymphoproliferative disease characterized by a progressive proliferation and accumulation of mature non-functional B-lymphocytes in peripheral blood, bone marrow and lymphoid tissue. Chemotherapy remains the backbone of modern frontline therapy for B-CLL patients, however, these patients have high variability in intra- and inter-individual responses to chemotherapy and this remains unpredictable at the individual patient level. Cytochrome P450 enzymes are monooxygenases, which play a crucial role in human physiology and are involved in drug and xenobiotic biotransformation. CYPs members also play a vital role in the bioactivation of cyclophosphamide (CPA), an alkylating agent prodrug, used in the treatment regimens of B-CLL. A variety of factors influence CYPs expression. Genetic factors including SNPs, has been shown to affect CYP expression and non-genetic factors such as age and the disease state. The current work aimed to study the association between the genetic polymorphisms of CYP1A1*2A, CYP2B6*9, CYP3A4*1B, CYP3A5*3, CYP2D6*3 and CYP2D6*6 and the susceptibility to B-CLL in the Egyptian population, as well as their association with the clinical outcome following cyclophosphamide chemotherapy. This case-control study with follow up that was conducted on 100 Egyptian cases newly diagnosed with B-CLL. The control group contained 100 age- and sex- healthy volunteers. At the disease diagnosis, physical examinations and radiological scans, IPT, bone marrow examination and cytogenetic analysis were performed for all the patients, along with complete blood count and some routine biochemical tests. Also, blood samples were aspirated for performing the molecular analyses, serum cytokines (IL-6 and TNF-α). All the molecular analyses of the studied SNPs were performed using PCR. Further, patients were indicated for receiving chemotherapy. Patients treated only with cyclophosphamide were followed up and the clinical outcome was recorded.