الفهرس 
B-CELL chrONIC LYMPHOCYTIC LEUKEMIAOnly 14 pages are availabe for public view
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Abstract
The B-cell chronic lymphocytic leukemia (CLL) is a disease with a very low proliferative activity. It is characterized by the accumulation of clonal B-lymphocytes that seem to be arrested in early G0/G1 phase of the cell-cycle. Although the pathogenesis of B-CLL remains largely unknown, several investigators have focused on the role of cytogenetic aberrations that may contribute to defective apoptosis, deregulation of cell-cycle regulatory genes and expansion of the malignant clone.
Although the survival time is variable, CLL is basically a long-lasting disease. Treatment decisions in the past relied on the clinical symptoms at diagnosis or progression. For prognosis, only indirect and relatively soft parameters (e.g. cell morphology, serum findings) could be considered. The easy and continuous access to the leukemic cells from the peripheral blood, together with the improvements in the molecular methodology led to completely novel understanding of the biologic background of this leukemia. It turned out that beside to the IgVH mutation status and CD38 expression, cytogenetic aberrations may fundamentally influence the outcome of the disease.
Clonal chromosomal aberrations are detected in about 40% of B-CLL patients. Recently, higher percentages were documented when using molecular techniques such as fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR) and comparative genomic hybridization (CGH).
The present study aimed to detect cases of chronic lymphocytic leukemia with deletions of chromosome 13q14 and / or p53 loci using FISH technique, to correlate the findings with clinical data of the cases and to evaluate the prognostic values of these markers.
The present study was carried out on 20 adult patients presented with CLL. They were selected from the Hematology / Oncology clinics of Ain Shams University Hospitals during the period from January 2008 to March 2009. Their ages ranged from 41 and 77 years with a median age of 61 years. All cases were studied at diagnosis before starting chemotherapy. FISH technique was done to all subjects included in the study using fluorophore labeled locus specific identifier ( LSI ) dual color probe applied on PB or BM samples for detection of 13q14 and / or 17p13 (p53) deletions.
In the current study, FISH revealed positive deletions involving only the 13q14 region in 4 cases (20%). It also yielded positive deletions involving only the p53 region in 4 cases (20%). Deletions involving both critical regions at 13q14 and 17p13 were found in 12 cases (60%).
For comparative statistical studies, the patients were divided into group I (patients with favorable outcome) and group II (patients with unfavorable outcome).There was a significant statistical difference as regards del 13q14 and p53 deletion. As regards del 13q14, there was a high statistical incidence in group I (2out of 7cases) as compared to group II (2out of 13cases) (p= 0.045). On the contrary, group II (4out of 13cases) showed a higher statistical incidence of p53 deletions in the comparison with group I (0 out of 4cases) (p= 0.039). However, no significant statistical difference was found as regards all clinical manifestations and other laboratory results among both groups (P >0.05).
There was a significant negative association between 13q14 deletion and LDH level (p= 0.040). Also, there was a significant association between p53 deletion and splenomegaly (p= 0.036). But, there was no correlation between 13q14 or p53 deletions and other parameters (P >0.05).
In a comparison done to determine the dominant clone in cases of both deletions, we found that in the 12 cases with (del13q14/del p53), the dominant clone was del13q in 6 cases and del p53 in 2 cases with the same cut-off used (10%) and about the same in 3 cases. One case showed only one clone of cells with both deletions. The mean age of cases with both deletions was 59.44 ± 10.19. While, the mean age of cases with deletion 13q14 was 56.67 ± 9.22.
In conclusion, studying the prognostic impact of 13q14 and 17p13 (p53) deletions on a wider scale of Egyptian CLL patients, using both CCA together with FISH, in a complementary fashion, is recommended to extend the range of cytogenetic analysis and overcome the pitfalls of both techniques. The development of molecular targeted therapeutic protocols for CLL patients, according to the result of their genetic analysis at diagnosis is also recommended. Deletion of 17p indicates the poorest outcome in CLL and lack of response to standard therapy; such patients should receive specially tailored therapy, preferably within clinical trials investigating alternative treatments and allogeneic stem cell transplantation.