الفهرس 
NON-HODGKIN LYMPHOMA
Diagnostic ApproachOnly 14 pages are availabe for public view
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Abstract
NHL comprises an extremely heterogeneous group of clonal lympho-proliferative disorders(LPD) that might be derived from either B-cell or T/NK-cell lineages. Within this broad term of NHL, numerous disease entities with variable clinical behavior and diverse molecular features were included.
The introduction of cytogenetic and molecular technologies have enriched the study of NHL, allowing a more global assessment of the different chromosomal alterations and genetic dysregulations underlying lymphomagenesis, as well as providing a new means for more exactly defining molecular hallmarks of distinct lymphoma subtypes.
Molecular pathogenesis of NHL represents a complex process involving the accumulation of multiple genetic lesions which include: the activation of proto-oncogens such as BCL1, BCL2, BCL6, c-MYC by chromosomal translocation, as well as inactivation of tumor suppressor genes such as TP53 by chromosomal deletion or mutation.
The BCL family members are proto-oncogenes that seem to be important regulators of lymphocyte function, differentiation and survival. BCL2 is an anti-apoptotic factor that is important for normal B-cell development and differentiation. BCL6 is another member of the BCL-family acts as a sequence-specific repressor of transcription with pivotal roles in B-cell activation, differentiation, inflammation and cell-cycle control. Deregulated expression of BCL2 and BCL6 as a result of chromosomal translocations has a marked effect on cell survival and function, with a potential to promote lymphomagenesis.
In light of these data, the present study aimed to detect BCL2 and BCL6 genes aberrations using FISH technique applied on different samples (BM aspirate, LN biopsy or BM trephine biopsy) in NHL patients and evaluate the prognostic significance of these genetic aberrations on the OS of NHL patients.
The present study was carried out on 46 newly diagnosed adults with NHL with the median age at diagnosis was 53 years (27 males and 19 females). Patients were followed up over a period of 11-24 months with a median of 17 months.
The studied patient population included 25 consecutive adults diagnosed with DLBCL (14 males and 11 females). Their ages ranged from 23-70 years, with a median age of 52 years. Another 21 consecutive FL patients were enrolled (13 males and 8 females). Their ages ranged from 39-67 years, with a median of 58 years.
Patients were diagnosed as having NHL on the basis of; full clinical history and thorough clinical examination, radiological examination and laboratory investigations including CBC, examination of PB stained smears, BM aspiration and examination of stained smears for detection of infiltration by 30% lymphoid cells of all nucleated BM cells, histopathological evaluation of LN core or paraffin-embedded BM trephine biopsy as well as flow cytometric immunophenotyping.
CCA using G-banding technique and FISH analysis using fluorophore-labeled locus specific identifier (LSI) break-apart rearrangements probes for BCL2 (18q21) and BCL6 (3q27) were applied to BM aspirates, BM trephine biopsy, or LN biopsy in patients without BM infiltration.
In the current work, Using FISH, BCL2 gene rearrangements were detected in 24% of patients with DLBCL and in 81% of FL patients whereas BCL6 gene rearrangements were detected in 36% of DLBCL patients and in 10% of FL patients. No significant association was found between these molecular markers and the clinicopathological features as well as standard prognostic factors in both groups of patients except for staging in DLBCL patients with BCL6 gene rearrangements.
Follow-up of the patients with NHL revealed that BCL2 positive patients displayed a high tendency for developing resistance, poor clinical outcome and a significantly shorter overall and disease-free survival times in DLBCL. A clear trend for a better response to therapy, favorable clinical outcome and a longer survival was found in BCL6 positive patients with DLBCL. Similar results were observed in patients with FL but the difference did not reach a significant level.In conclusion, BCL2 and BCL6 gene rearrangements occur frequently in NHL and could be considered independent prognostic factors that carry different impacts on treatment response and clinical outcome of patients. Thereafter, the use of these molecular markers in NHL would be recommended to guide therapeutic regimens.