Epigenetic mechanisms in the initiation of hematological malignancies

Ali Maleki; Saied Kaviani; Mehrdad Noruzinia; Majid Farshdusti-Hagh; Zeinab Kaviani; kamran mansouri

Zahedan Journal of Research in Medical Sciences

The Official Journal of Zahedan University of Medical Sciences

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Epigenetic mechanisms in the initiation of hematological malignancies

Author(s):

Ali Maleki¹,

Saied Kaviani^1,*,

Mehrdad Noruzinia²,

Majid Farshdusti-Hagh³,

Zeinab Kaviani⁴,

kamran mansouri¹

1MSc of Hematology, Medical Biology Research Center Kermanshah University of Medical Sciences, Kermanshah, Iran.

2Assistant Professor of Hematology and Medical genetics, Tarbiat Modares University, Tehran, Iran.

3PhD student of Hematology, Tarbiat Modares University, Tehran, Iran.

4MD student, Tehran University of Medical Sciences, Tehran, Iran.

Zahedan Journal of Research in Medical Sciences:Vol. 13, issue 5; e93905

Published online:May 12, 2011

Article type:Review Article

Received:Jan 04, 2010

Accepted:Jan 04, 2011

How to Cite:Ali MalekiSaied KavianiMehrdad NoruziniaMajid Farshdusti-HaghZeinab Kavianikamran mansouriet al.Epigenetic mechanisms in the initiation of hematological malignancies.Zahedan J Res Med Sci.13(5):e93905.

Abstract

Background: Cancer development is not restricted to the genetic changes, but also to epigenetic changes. Epigenetic processes are very important in the development of hematological malignancies. The main epigenetic alterations are aberrations in DNA methylation, post-translational modifications of histones, chromatin remodeling and microRNAs patterns, and these are associated with tumor genesis. All the various cellular pathways contributing to the neoplastic phenotype are affected by epigenetic genes in cancer. These pathways can be explored as biomarkers in clinical use for early detection of disease, malignancy classification and response to treatment with classical chemotherapy agents and epigenetic drugs.

Materials and Method: A literature review was performed using PUBMED from 1985 to 2008. Cross referencing of discovered articles was also reviewed.

Results: In chronic lymphocytic leukemia, regional hypermethylation of gene promoters leads to gene silencing. Many of these genes have tumor suppressor phenotypes. In myelodysplastic syndrome (MDS), CDKN2B (alias, P15), a cyclin-dependent kinase inhibitor that negatively regulates the cell cycle, has been shown to be hypermethylated in marrow stem (CD34+) cells in patients with MDS. At present both Vidaza and Decitabine (DNA methyltransferase inhibitors) are approved for the treatment of MDS.

Conclusion: Unlike mutations or deletions, DNA hypermethylation and histone deacetylation are potentially reversible by pharmacological inhibition, therefore those epigenetic changes have been recognized as promising novel therapeutic targets in hematopoietic malignances. In this review, we discussed molecular mechanisms of epigenetics, epigenetic changes in hematological malignancies and epigenetic based treatments.

Keywords

Epigenetic

hematological neoplasms

methylation

histone

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