scholarly journals Hypermethylation Analysis of p16INK4a and p15INK4b Promoters in Chronic Lymphocytic Leukaemia Patients and Normal Individuals

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Amira M ◽  
Sarina S ◽  
Rosline H ◽  
Azlan H ◽  
Muhammad Farid J ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Asian Population ◽  
Tumour Suppressor Genes ◽  
European Descent ◽  
Specific Pcr ◽  
Normal Individuals ◽  
Sequencing Method ◽  
Different Populations ◽  
Larger Sample

Introduction: Chronic Lymphocytic Leukaemia (CLL) is a common type of leukaemia in persons of predominantly European descent but is rare in the Asian population. Disparities in CLL incidence among people of Asian and European descent may be related to the genetic make-up of the two different populations. Hypermethylation event might be one of the silencing mechanisms that inactivate the tumour suppressor genes in CLL. The aim of this study was to determine the hypermethylation status of p16INK4a and p15INK4b among CLL patients and normal individuals. Materials & Methods: A total of 25 CLL patients and 25 normal individuals were recruited for this study and their genomic DNA were extracted from the peripheral blood. The hypermethylation status of p16INK4a and p15INK4b were determined using Methylation Specific-PCR (MS-PCR) whereas DNA sequencing method was applied to selected samples for validation of the MS-PCR results. We also evaluated the association between hypermethylation of these genes with the clinical and demographic characteristics of each group of subjects. Results: Among the CLL patients, p15INK4b partialmethylation occurred in 6 (24%) subjects while methylation occurred in 1 (4%) subject. All the remaining patients were unmethylated at p15INK4b. All the samples showed unmethylation at p16INK4a. Statistically significant associations were found between p15INK4b hypermethylation with the presence of CLL (p=0.01) and with race (p=0.02). Conclusion: Further study using a larger sample size is warranted to explore the significance of DNA methylation incidence among the CLL patients of the Malaysian population. Hence, we suggest that hypermethylation at p15INK4b has a huge influence that kick-starts CLL disease among Malaysians and MS-PCR technique is applicable to be used in methylation study.

Epigenetic dysregulation of the Wnt signalling pathway in chronic lymphocytic leukaemia

2008 ◽  
Vol 61 (11) ◽  
pp. 1214-1219 ◽  
Author(s):  
C S Chim ◽  
R Pang ◽  
R Liang
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
B Lymphocytes ◽  
Peripheral Blood ◽  
Lymphocytic Leukaemia ◽  
Methylation Status ◽  
Wnt Signalling ◽  
Constitutive Activation ◽  
Specific Pcr ◽  
Wnt Inhibitor ◽  
Inhibitor Genes

Background:Wnt signalling has recently been implicated in the pathogenesis of cancer.Methods:This study investigated the activity of Wnt signalling in peripheral blood chronic lymphocytic leukaemia (CLL) lymphocytes, and the methylation status of seven soluble Wnt antagonist genes, including WIF1, DKK3, APC, SFRP1, SFRP2, SFRP4 and SFRP5, by using methylation-specific PCR in the peripheral blood CLL lymphocytes and bone marrow samples of patients with CLL at diagnosis.Results:In the peripheral blood CLL lymphocytes, constitutive activation of Wnt signalling was detected, associated with hypermethylation of the soluble Wnt inhibitor genes. In the diagnostic CLL marrow samples, methylation of the seven genes was detected in up to 36.4% of samples. Moreover, 23 (52.3%) patients had methylation of at least one of the seven genes, of whom 14 (60.8%) had methylation of two or more Wnt inhibitor genes. Apart from an association of advanced age with DKK3 methylation, there was no association of gene hypermethylation with either clinical characteristics (including age, gender, lymphocyte count at diagnosis, Rai stage and poor-risk karyotype) or survival.Conclusion:Wnt signalling is constitutively activated in CLL B lymphocytes in association with methylation of multiple soluble Wnt antagonist genes. Methylation of these soluble Wnt antagonist genes, occasionally multiple genes, in primary CLL marrow samples suggests an important role in CLL pathogenesis. Moreover, this study underscored the importance of studying methylation of a panel of, but not individual, genes regulating a cellular pathway.

Autologous T lymphocytes recognize the tumour-derived immunoglobulin VH-CDR3 region in patients with B-cell chronic lymphocytic leukaemia

2000 ◽  
Vol 111 (1) ◽  
pp. 230-238 ◽  
Author(s):  
Mohammad Reza Rezvany ◽  
Mahmood Jeddi-Tehrani ◽  
Hodjattallah Rabbani ◽  
Ulla Ruden ◽  
Lennart Hammarstrom ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Chronic Lymphocytic Leukaemia ◽  
B Cell ◽  
Lymphocytic Leukaemia ◽  
Cell Chronic Lymphocytic Leukaemia ◽  
Cdr3 Region

Pharmacokinetics of Chlorambucil in Patients with Chronic Lymphocytic Leukaemia: Comparison of Different Days, Cycles and Doses

2000 ◽  
Vol 87 (5) ◽  
pp. 223-228 ◽  
Author(s):  
Raija Silvennoinen ◽  
Kimmo Malminiemi ◽  
Outi Malminiemi ◽  
Erkki Seppala ◽  
Juhani Vilpo
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia

The Local Sanarelli-Shwartzman Phenomenon in Rats Induced by Human Leukaemic Cells

1973 ◽  
Vol 29 (02) ◽  
pp. 353-362
Author(s):  
J Lisiewicz ◽  
A Pituch ◽  
J. A Litwin
Keyword(s):  
Chronic Lymphocytic Leukaemia ◽  
Intravenous Injection ◽  
Peripheral Blood ◽  
Lymphocytic Leukaemia ◽  
Acute Myeloblastic Leukaemia ◽  
Demarcation Line ◽  
E Coli ◽  
Leukaemic Cells ◽  
Shwartzman Phenomenon

SummaryThe local Sanarelli-Shwartzman phenomenon (SSP-L) in the skin of 30 rats was induced by an intr a cutaneous sensitizing injection of leukaemic leucocytes isolated from the peripheral blood of patients with chronic lymphocytic leukaemia (CLL), acute myeloblastic leukaemia (AL) and chronic granulocytic leukaemia (CGL) and challenged by an intravenous injection of 100(μ of E. coli endotoxin. SSP-L was observed in 7 rats after injection of CLL lymphocytes and in 6 and 2 rats after AL myeloblasts and the CGL granulocytes, respectively. The lesions in the skin after AL myeloblasts appeared in a shorter time and were of longer duration compared with those observed after CLL lymphocytes and CGL granulocytes. Histologically, the lesions consisted of areas of destruction in the superficial layers of the skin ; the demarcation line showed the presence of neutrophils, macrophages and erythrocytes. Haemorrhages and fibrin deposits near the demarcation line were larger after injection of CLL lymphocytes and AL myeloblasts than after CGL granulocytes. The possible role of leucocyte procoagulative substances in the differences observed have been discussed.

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