Differential Analysis of Genetic, Epigenetic, and Cytogenetic Abnormalities in AML
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...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-01-01
|
| Series: | International Journal of Genomics |
| Online Access: | http://dx.doi.org/10.1155/2017/2913648 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832562261493809152 |
|---|---|
| author | Mirazul Islam Zahurin Mohamed Yassen Assenov |
| author_facet | Mirazul Islam Zahurin Mohamed Yassen Assenov |
| author_sort | Mirazul Islam |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-475fdfbc0eb549b0bed382424b213019 |
| institution | Kabale University |
| issn | 2314-436X 2314-4378 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Genomics |
| spelling | doaj-art-475fdfbc0eb549b0bed382424b2130192025-02-03T01:23:04ZengWileyInternational Journal of Genomics2314-436X2314-43782017-01-01201710.1155/2017/29136482913648Differential Analysis of Genetic, Epigenetic, and Cytogenetic Abnormalities in AMLMirazul Islam0Zahurin Mohamed1Yassen Assenov2Pharmacogenomics Lab, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, MalaysiaPharmacogenomics Lab, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, MalaysiaComputational Epigenomics Group, Division of Epigenomics and Cancer Risk Factor, German Cancer Research Center, Heidelberg, GermanyAcute 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.http://dx.doi.org/10.1155/2017/2913648 |
| spellingShingle | Mirazul Islam Zahurin Mohamed Yassen Assenov Differential Analysis of Genetic, Epigenetic, and Cytogenetic Abnormalities in AML International Journal of Genomics |
| title | Differential Analysis of Genetic, Epigenetic, and Cytogenetic Abnormalities in AML |
| title_full | Differential Analysis of Genetic, Epigenetic, and Cytogenetic Abnormalities in AML |
| title_fullStr | Differential Analysis of Genetic, Epigenetic, and Cytogenetic Abnormalities in AML |
| title_full_unstemmed | Differential Analysis of Genetic, Epigenetic, and Cytogenetic Abnormalities in AML |
| title_short | Differential Analysis of Genetic, Epigenetic, and Cytogenetic Abnormalities in AML |
| title_sort | differential analysis of genetic epigenetic and cytogenetic abnormalities in aml |
| url | http://dx.doi.org/10.1155/2017/2913648 |
| work_keys_str_mv | AT mirazulislam differentialanalysisofgeneticepigeneticandcytogeneticabnormalitiesinaml AT zahurinmohamed differentialanalysisofgeneticepigeneticandcytogeneticabnormalitiesinaml AT yassenassenov differentialanalysisofgeneticepigeneticandcytogeneticabnormalitiesinaml |