Differential Analysis of Genetic, Epigenetic, and Cytogenetic Abnormalities in AML

Islam, M. and Mohamed, Z. and Assenov, Y. (2017) Differential Analysis of Genetic, Epigenetic, and Cytogenetic Abnormalities in AML. International Journal of Genomics, 2017. pp. 1-13. ISSN 2314-436X, DOI https://doi.org/10.1155/2017/2913648.

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Abstract

Acute myeloid leukemia (AML) is a haematological malignancy characterized by the excessive proliferation of immature myeloid cells coupled with impaired differentiation. Many AML cases have been reported without any known cytogenetic abnormalities and carry no mutation in known AML-associated driver genes. In this study, 200 AML cases were selected from a publicly available cohort and differentially analyzed for genetic, epigenetic, and cytogenetic abnormalities. Three genes (FLT3, DNMT3A, and NPMc) are found to be predominantly mutated. We identified several aberrations to be associated with genome-wide methylation changes. These include Del (5q), T (15; 17), and NPMc mutations. Four aberrations—Del (5q), T (15; 17), T (9; 22), and T (9; 11)—are significantly associated with patient survival. Del (5q)-positive patients have an average survival of less than 1 year, whereas T (15; 17)-positive patients have a significantly better prognosis. Combining the methylation and mutation data reveals three distinct patient groups and four clusters of genes. We speculate that combined signatures have the better potential to be used for subclassification of AML, complementing cytogenetic signatures. A larger sample cohort and further investigation of the effects observed in this study are required to enable the clinical application of our patient classification aided by DNA methylation.

Item Type:	Article
Funders:	UNSPECIFIED
Uncontrolled Keywords:	Differential Analysis; Genetic; Epigenetic; Cytogenetic Abnormalities; AML
Subjects:	R Medicine R Medicine > RM Therapeutics. Pharmacology
Divisions:	Faculty of Medicine
Depositing User:	Ms. Juhaida Abd Rahim
Date Deposited:	10 Jul 2017 08:05
Last Modified:	10 Jul 2017 08:05
URI:	http://eprints.um.edu.my/id/eprint/17470

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