Common Polymorphism G(-248)A in the Promoter Region of the bax Gene Results in Significantly Shorter Survival in Patients With Chronic Lymphocytic Leukemia Once Treatment Is Initiated

2005 ◽  
Vol 23 (7) ◽  
pp. 1514-1521 ◽  
Author(s):  
Jane Starczynski ◽  
Chris Pepper ◽  
Guy Pratt ◽  
Laura Hooper ◽  
Alun Thomas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Single Nucleotide Polymorphism ◽  
Chronic Lymphocytic Leukemia ◽  
Promoter Region ◽  
Lymphocytic Leukemia ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Bax Protein ◽  
Significant Difference ◽  
Bax Gene

Purpose Chronic lymphocytic leukemia (CLL) is characterized by the development of drug resistance. The underlying biologic and genetic reasons for this resistance are complex, but the bcl-2 gene family seems to play a critical role. This retrospective study assessed the clinical impact of a common single nucleotide polymorphism of the pro-apoptotic bax gene in patients with chronic lymphocytic leukemia. Patients and Methods The frequency of the novel polymorphism, G(−248)A, in the promoter region of the bax gene and bax protein expression was assessed in 203 CLL patients. The results were correlated with clinical outcome. Results The polymorphism was found in 23% of the CLL cohort and 15% of normal controls with no significant difference in allele frequency between the two groups (P = .15). It was associated with lower Bax protein expression and a shorter overall survival, especially in the treated patient group (P = .03). Furthermore, the adverse impact of the polymorphism was accentuated when comparing survival from the date of first treatment rather than diagnosis (P = .012). No significant difference in age at diagnosis, stage of disease at presentation, lymphocyte doubling time, time to first treatment, or progression-free survival were observed. Conclusion The presence of this single nucleotide polymorphism in CLL critically influences the response to treatment and overall survival. Given the relatively high prevalence of this polymorphism in the normal population, further prospective studies in CLL and other human malignancies are indicated.

scholarly journals TP53 Gene 72 Arg/Pro (rs1042522) Single Nucleotide Polymorphism Contribute to Increase the Risk of B-Chronic Lymphocytic Leukemia in the Sudanese Population

2019 ◽  
Vol 20 (5) ◽  
pp. 1579-1585
Author(s):  
Ameen Abdulaziz Mohammed Basabaeen ◽  
Enaam Abdalrhman Abdelgader ◽  
Ebtihal Ahmed Babekir ◽  
Saadia Osman Abdelrahim ◽  
Nada Hassan Eltayeb ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Chronic Lymphocytic Leukemia ◽  
Tp53 Gene ◽  
Lymphocytic Leukemia ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide

scholarly journals MicroRNA-196a2 single nucleotide polymorphism rs11614913 in Egyptian patients with chronic lymphocytic leukemia

2019 ◽  
Vol 7 (1) ◽  
pp. 17-20
Author(s):  
Akram Deghady ◽  
Reham Abo Elwafa ◽  
Manal AE Lsorady, ◽  
Darine Elbana
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Control Group ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Rna Molecules ◽  
Increased Risk ◽  
Egyptian Patients ◽  
Apoptosis Regulation

Background: MicroRNAs are recently identified class of small single stranded RNA molecules of 21-23 nucleotides that regulate gene expression at the posttranscriptional level. Chronic lymphocytic leukemia (CLL) is characterized by a typical defect in apoptosis resulting in accumulation of mature resting B cells within the peripheral blood, bone marrow and lymphoid organs. One of the relevant microRNAs to CLL is microRNA-196a2, as its potential targets of action include genes involved in apoptosis regulation. The single nucleotide polymorphism (SNP) in microRNA-196a2 rs11614913 C/T has been implicated as possible biomarker associated with multiple kinds of cancers. While multiple recent studies showed that genetic polymorphisms play an influential role in CLL susceptibility, the role of microRNA-196a2 SNP rs11614913in CLL remains elusive. Patients and methods: The present study was conducted on 40 newly diagnosed Egyptian CLL patients and 40 control subjects. Genotyping of microRNA-196a2 SNP rs11614913 was performed by real-time PCR. Results: The CC genotype was found in 55% of CLL patients versus 12.5% of the controls.On the other handthe TT and TC genotypes were significantly predominant in the control group compared to CLL patients with frequencies of 25% and 62.5% versus 10% and 35% respectively (p<0.001). The C allele carriers were found to have 3.38 fold increased risk for development of CLL (OR=3.38, CI=1.75–6.56) while the T allele seems to be protective against CLL (OR=0.29, CI=0.15–0.57). Conclusion: We could conclude that the CC genotype and the C allele of miR-1962a SNP rs3217927are implicated in the risk of CLL development in Egyptian patients while the T allele has a protective effect. However, additional well-designed large studies are required for the validation of these associations

scholarly journals Cryptic Unbalanced Chromosomal Changes in a Case of Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (CLL/SLL) Identified By Single Nucleotide Polymorphism (SNP) Microarray, but Not By Conventional Karyotyping

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5649-5649
Author(s):  
Peter C. Kurniali ◽  
Anas Al-Janadi ◽  
Hongyan Chai ◽  
Sainan Wei
Keyword(s):  
Bone Marrow ◽  
Single Nucleotide Polymorphism ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Nucleotide Polymorphism ◽  
Small Lymphocytic Lymphoma ◽  
Balanced Translocation ◽  
Single Nucleotide ◽  
Snp Microarray ◽  
Cytogenetic Studies

Abstract Genomic abnormalities have been widely used to diagnose and provide prognostic significance in many hematologic malignancies (HM). The use of conventional G-banded chromosome and fluorescence in situ hybridization (FISH) analyses sometimes fail to detect genomic abnormalities due to the need for actively dividing cells and lower resolution of chromosome analysis (G-banded), as well as the inability to detect copy number of neutral loss of heterozygocity (G-banded and FISH). The addition of single nucleotide polymorphism (SNP) microarray has been shown to increase the detection rate of genomic abnormalities in HM. We report a 62-year-old Caucasian woman with a diagnosis of chronic lymphocytic leukemia /small lymphocytic lymphoma (CLL/SLL). Cytogenetic studies done at the time when she required initial treatment in 2011 showed a balanced translocation between chromosomes 6 and 13 {46,XX,t(6;13)(p10;q10)[10]/46,XX[10]}. She was treated with bendamustine plus rituximab and achieved complete response. In 2013, she developed worsening of anemia and marked lymphocytosis. Blood and bone marrow examination showed polymphocytic transformation. G-banded cytogenetic studies again showed a balanced translocation between chromosomes 6 and 13 (same as in 2011). However, FISH analysis detected a deletion of 13q. G-banded cytogenetic study was re-examined and showed balanced translocation: 46,XX,t(6;13)(p10;q10)[10]/46,XX[10]. Re-analysis of bone marrow cytogenetic from 2011 also suggested possible deletion of 13q, but the resolution was poor. Cytogenetic microarray validation was performed and revealed not only deletions of 13q14.2q14.3, but also 6p21.1p21.1. Karyotypic changes of chromosome 6 have been associated with prolymphocytic transformation in CLL/SLL. Deletion of 13q14.3 usually carries good prognosis in CLL/SLL. However, additional abnormalities and deletions of different sizes of 13q reportedly cooperate to change its favorable value. An accurate cytogenetic analysis may be useful in aiding in diagnosis, prognosis, and possibly therapy. Our findings suggest that microarray analysis is a suitable companion test to G-banded chromosome and FISH analyses, especially in CLL/SLL. Disclosures No relevant conflicts of interest to declare.

Genomewide Linkage Analysis of Chronic Lymphocytic Leukemia by Use of a High-Density Single Nucleotide Polymorphism Assay Containing 11,555 Markers.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1904-1904
Author(s):  
Gabrielle S. Sellick ◽  
Ruth Allinson ◽  
Estella Matutes ◽  
Martin Yuille ◽  
Daniel Catovsky ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Chronic Lymphocytic Leukemia ◽  
Linkage Analysis ◽  
Familial Aggregation ◽  
High Density ◽  
Lymphocytic Leukemia ◽  
Nucleotide Polymorphism ◽  
Degree Relative ◽  
Single Nucleotide ◽  
Genomewide Linkage

Abstract A genetic basis for chronic lymphocytic leukemia (CLL) is indicated by studies demonstrating that the lifetime risk of developing the disease increases by a factor of seven when at least one first-degree relative is affected. Significant familial aggregation of CLL has been demonstrated, but the mode of inheritance is unknown. To date no genes which when mutated have unequivocally been shown to confer susceptibility to the disease. We have collected clinical data and biospecimens from 370 families comprising of at least two affected family members with CLL. Of these, samples from two or more individuals from 100 families were informative for linkage analysis. To identify a predisposition locus for CLL a high-density single nucleotide polymorphism (SNP)-based genomewide linkage search was conducted using the GeneChip Mapping 10k Xba array containing 11,555 SNP markers (Affymetrix Inc., Santa Clara, CA). Multipoint LOD scores were calculated, assuming both dominant and recessive inheritance and allowing for increased penetrance with age and genetic heterogeneity. Non-parametric linkage scores were also calculated. The results from these analyses will be presented.

BCL2 expression in chronic lymphocytic leukemia: lack of association with the BCL2 −938A>C promoter single nucleotide polymorphism

Blood ◽  
2008 ◽  
Vol 111 (2) ◽  
pp. 874-877 ◽  
Author(s):  
Aneela Majid ◽  
Olga Tsoulakis ◽  
Renata Walewska ◽  
Stefan Gesk ◽  
Reiner Siebert ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Chronic Lymphocytic Leukemia ◽  
Protein Expression ◽  
Lymphocytic Leukemia ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Protein Levels ◽  
Bcl2 Protein ◽  
High Level ◽  
Bcl2 Expression

High-level BCL2 expression is seen in most patients with chronic lymphocytic leukemia (CLL) in the absence of BCL2 chromosomal translocation. A single nucleotide polymorphism (SNP; −938C>A) within an inhibitory region of the BCL2 promoter has been reported to regulate BCL2 protein expression and to be associated with adverse prognostic features in CLL. We screened 276 patients with CLL for this SNP and 100 patients by quantitative Western blot for BCL2 expression. In contrast to the previous report, we found no association with BCL2 protein levels or with any clinical or laboratory parameters. BCL2 protein levels remained constant in 10 individual patients at different time points. A total of 19 patients with the lowest levels of BCL2 protein expression were biologically and clinically heterogeneous; 5 patients exhibited high-level BCL2 RNA expression and 4 were fludarabine resistant. BCL2 protein levels in CLL reflect a complex interplay of transcriptional and posttranscriptional controls, but do not appear to be associated with the −938C>A promoter SNP.

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