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.
Highlights
Acute myeloid leukemia (AML) is a haematological disorder characterized by excessive proliferation of undifferentiated myeloid cells [1] in the bone marrow that infiltrate the liver, spleen, lymph node, and circulating blood [2]
To analyze the AML data generated by The Cancer Genome Atlas (TCGA), we directly accessed and downloaded the raw data, using the “Data Matrix” tool provided by TCGA Data Portal
In the primary study cohort, a total of 200 AML patients were listed in the TCGA database
Summary
AML is a haematological disorder characterized by excessive proliferation of undifferentiated myeloid cells [1] in the bone marrow that infiltrate the liver, spleen, lymph node, and circulating blood [2]. This cancer type progresses rapidly and is relatively fatal due to acquired genetic and/or cytogenetic aberrations. A significant proportion of the patients carry no reported genetic mutations in any known AML-associated driver genes [7, 8]. These findings clearly indicate that there are other elements predisposing to and driving the disease in the case of cytogenetically normal AML (CN-AML)
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