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International Journal of Genomics
Volume 2017, Article ID 2913648, 13 pages
Research Article

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

1Pharmacogenomics Lab, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
2Computational Epigenomics Group, Division of Epigenomics and Cancer Risk Factor, German Cancer Research Center, Heidelberg, Germany
3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

Correspondence should be addressed to Zahurin Mohamed; and Yassen Assenov; ed.zfkd@vonessa.y

Received 14 November 2016; Revised 21 March 2017; Accepted 18 April 2017; Published 20 June 2017

Academic Editor: Brian Wigdahl

Copyright © 2017 Mirazul Islam et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.