Understanding the impact of DNMT3A Knockout on K562 cell sensitivity towards epigenetic drug treatments

DNMT3A mutation has been seen as a marker of acute myeloid leukaemia. DNMT3A mutation can cause genome methylation changes and the reliance on other epigenetic modifiers including other methyltransferases for maintaining regular gene expression for survival. The loss of the remaining epigenetic modi...

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Main Author: Mah, Lian-Khye
Other Authors: Melissa Jane Fullwood
Format: Final Year Project
Language:English
Published: 2019
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Online Access:http://hdl.handle.net/10356/78545
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-785452023-02-28T18:04:15Z Understanding the impact of DNMT3A Knockout on K562 cell sensitivity towards epigenetic drug treatments Mah, Lian-Khye Melissa Jane Fullwood School of Biological Sciences DRNTU::Science::Biological sciences DNMT3A mutation has been seen as a marker of acute myeloid leukaemia. DNMT3A mutation can cause genome methylation changes and the reliance on other epigenetic modifiers including other methyltransferases for maintaining regular gene expression for survival. The loss of the remaining epigenetic modifiers may cause further epigenetic destabilisation that is incompatible with viability. Therefore this study proposes that the altered epigenetic landscape of DNMT3A knockout cells can be exploited for regulating cell proliferation by exposing the cells to epigenetic drugs. This study utilises a 13bp deletion in exon 7 of the DNMT3A gene to represent mutated DNMT3A function. The cells were then exposed to epigenetic drugs such as Azacitidine, JQ1, and GSK343 that are able to inhibit epigenetic modifiers including methyltransferases. The IC50 was calculated from cell viability values using CellTiter-Glo cell viability assay to determine drug sensitivity. The data derived showed that DNMT3A knockout and Control cells portrayed similar sensitivities towards epigenetic drugs. This shows that the changes in methylation state from the loss of DNMT3A function may not have a significant impact on drug sensitivity. Future studies including the use of other therapeutic mechanisms should be conducted to understand the extent of drug sensitivities in DNMT3A mutant cells. Bachelor of Science in Biological Sciences 2019-06-21T05:56:49Z 2019-06-21T05:56:49Z 2019 Final Year Project (FYP) http://hdl.handle.net/10356/78545 en Nanyang Technological University 41 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
spellingShingle DRNTU::Science::Biological sciences
Mah, Lian-Khye
Understanding the impact of DNMT3A Knockout on K562 cell sensitivity towards epigenetic drug treatments
description DNMT3A mutation has been seen as a marker of acute myeloid leukaemia. DNMT3A mutation can cause genome methylation changes and the reliance on other epigenetic modifiers including other methyltransferases for maintaining regular gene expression for survival. The loss of the remaining epigenetic modifiers may cause further epigenetic destabilisation that is incompatible with viability. Therefore this study proposes that the altered epigenetic landscape of DNMT3A knockout cells can be exploited for regulating cell proliferation by exposing the cells to epigenetic drugs. This study utilises a 13bp deletion in exon 7 of the DNMT3A gene to represent mutated DNMT3A function. The cells were then exposed to epigenetic drugs such as Azacitidine, JQ1, and GSK343 that are able to inhibit epigenetic modifiers including methyltransferases. The IC50 was calculated from cell viability values using CellTiter-Glo cell viability assay to determine drug sensitivity. The data derived showed that DNMT3A knockout and Control cells portrayed similar sensitivities towards epigenetic drugs. This shows that the changes in methylation state from the loss of DNMT3A function may not have a significant impact on drug sensitivity. Future studies including the use of other therapeutic mechanisms should be conducted to understand the extent of drug sensitivities in DNMT3A mutant cells.
author2 Melissa Jane Fullwood
author_facet Melissa Jane Fullwood
Mah, Lian-Khye
format Final Year Project
author Mah, Lian-Khye
author_sort Mah, Lian-Khye
title Understanding the impact of DNMT3A Knockout on K562 cell sensitivity towards epigenetic drug treatments
title_short Understanding the impact of DNMT3A Knockout on K562 cell sensitivity towards epigenetic drug treatments
title_full Understanding the impact of DNMT3A Knockout on K562 cell sensitivity towards epigenetic drug treatments
title_fullStr Understanding the impact of DNMT3A Knockout on K562 cell sensitivity towards epigenetic drug treatments
title_full_unstemmed Understanding the impact of DNMT3A Knockout on K562 cell sensitivity towards epigenetic drug treatments
title_sort understanding the impact of dnmt3a knockout on k562 cell sensitivity towards epigenetic drug treatments
publishDate 2019
url http://hdl.handle.net/10356/78545
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