Hypermethylation Analysis of p16INK4a and p15INK4b Promoters in Chronic Lymphocytic Leukaemia Patients and Normal Individuals
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.
How to Cite
All material submitted for publication is assumed to be submitted exclusively to the IIUM Medical Journal Malaysia (IMJM) unless the contrary is stated. Manuscript decisions are based on a double-blinded peer review process. The Editor retains the right to determine the style and if necessary, edit and shorten any material accepted for publication.
IMJM retain copyright to all the articles published in the journal. All final ‘proof’ submissions must be accompanied by a completed Copyright Assignment Form, duly signed by all authors. The author(s) or copyright owner(s) irrevocably grant(s) to any third party, in advance and in perpetuity, the right to use, reproduce or disseminate the research article in its entirety or in part, in any format or medium, provided that no substantive errors are introduced in the process, proper attribution of authorship and correct citation details are given, and that the bibliographic details are not changed. If the article is reproduced or disseminated in part, this must be clearly and unequivocally indicated.