DNMT3A intragenic hypomethylation is associated with adverse prognosis in acute myeloid leukemia

Zhang, Yingying; Yao, Dong‐ming; Zhu, Xiaowen; Zhou, Jing‐Dong; Ma, Ji‐chun; Yang, Jing; Wen, Xiang‐mei; Guo, Hong; Jiang, Lin; Qian, Jun

doi:10.1016/j.leukres.2015.06.015

Cited by 4 publications

(1 citation statement)

References 41 publications

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“…There are different patterns of DNMT3A methylation in AML cases. In bone marrow, mononucleotide cells in AML showed significant hypomethylation of DNMT3A [44], whereas in peripheral blood cells, this gene was found hypermethylated [45]. We can say that aberrant DNMT3A methylation would be an independent negative prognostic factor in AML.…”

Section: Discussionmentioning

confidence: 99%

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

Islam

Mohamed

Assenov

2017

International Journal of Genomics

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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.

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Section: Discussionmentioning

confidence: 99%

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

Islam

Mohamed

Assenov

2017

International Journal of Genomics

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Down-regulation of lncRNA NEAT1 regulated by miR-194-5p/DNMT3A facilitates acute myeloid leukemia

Duan

Tian

et al. 2020

Blood Cells, Molecules, and Diseases

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Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies

Zhao

Zhou

Yang

et al. 2023

Sig Transduct Target Ther

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Hematologic malignancies are one of the most common cancers, and the incidence has been rising in recent decades. The clinical and molecular features of hematologic malignancies are highly heterogenous, and some hematologic malignancies are incurable, challenging the treatment, and prognosis of the patients. However, hematopoiesis and oncogenesis of hematologic malignancies are profoundly affected by epigenetic regulation. Studies have found that methylation-related mutations, abnormal methylation profiles of DNA, and abnormal histone deacetylase expression are recurrent in leukemia and lymphoma. Furthermore, the hypomethylating agents and histone deacetylase inhibitors are effective to treat acute myeloid leukemia and T-cell lymphomas, indicating that epigenetic regulation is indispensable to hematologic oncogenesis. Epigenetic regulation mainly includes DNA modifications, histone modifications, and noncoding RNA-mediated targeting, and regulates various DNA-based processes. This review presents the role of writers, readers, and erasers of DNA methylation and histone methylation, and acetylation in hematologic malignancies. In addition, this review provides the influence of microRNAs and long noncoding RNAs on hematologic malignancies. Furthermore, the implication of epigenetic regulation in targeted treatment is discussed. This review comprehensively presents the change and function of each epigenetic regulator in normal and oncogenic hematopoiesis and provides innovative epigenetic-targeted treatment in clinical practice.

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DNMT3A intragenic hypomethylation is associated with adverse prognosis in acute myeloid leukemia

Cited by 4 publications

References 41 publications

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

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

Down-regulation of lncRNA NEAT1 regulated by miR-194-5p/DNMT3A facilitates acute myeloid leukemia

Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies

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