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postgraduate thesis: DNA methylation patterns in t(8;21) acute myeloid leukemia patients
Title | DNA methylation patterns in t(8;21) acute myeloid leukemia patients |
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Authors | |
Issue Date | 2011 |
Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
Citation | Ho, S. [何肇騏]. (2011). DNA methylation patterns in t(8;21) acute myeloid leukemia patients. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4715138 |
Abstract | Acute myeloid leukemia (AML) is a heterogeneous disease both clinically and
biologically. Approximately 55% of AML harbour karyotypic changes, and one of the most common chromosomal aberrations is the t(8;21)(q22;q22), which leads to the AML1-ETO fusion protein. Previous studies have found that this fusion protein recruits the N-CoR/mSin3A/HDAC complex, thereby acts as a transcriptional repressor. Recently, DNA methylation array studies have shown that DNA methylation patterns can stratify AML cases into different subgroups, and some of these correspond to certain chromosomal abnormalities, such as the t(8;21). These findings suggest a possible link between the fusion transcript AML1-ETO and epigenetic modifications. Additionally, c-kit mutations have emerged as an important disease modifier in the t(8;21) AML and are correlated with poor overall survival and event free survival in patients with t(8;21) AML. We therefore sought to investigate whether there are different DNA methylation patterns in t(8;21) AML with or without c-kit mutations. In our series, 52.2% of the t(8;21) AMLs harbored c-kit mutations, which were correlated with poor event free survival. We next performed pyrosequencing on a selected panel of genes and pinpointed the THBS4 and PAWR genes as hypermethylated in their promoter CpG islands in 86.4% and 59.1% of the t(8;21) AML patients, respectively. These data suggest that THBS4 and PAWR may be important in the pathogenesis of t(8;21) AML. |
Degree | Master of Philosophy |
Subject | DNA - Methylation. Acute myeloid leukemia - Genetic aspects. |
Dept/Program | Pathology |
Persistent Identifier | http://hdl.handle.net/10722/179880 |
HKU Library Item ID | b4715138 |
DC Field | Value | Language |
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dc.contributor.author | Ho, Siu-ki. | - |
dc.contributor.author | 何肇騏. | - |
dc.date.issued | 2011 | - |
dc.identifier.citation | Ho, S. [何肇騏]. (2011). DNA methylation patterns in t(8;21) acute myeloid leukemia patients. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4715138 | - |
dc.identifier.uri | http://hdl.handle.net/10722/179880 | - |
dc.description.abstract | Acute myeloid leukemia (AML) is a heterogeneous disease both clinically and biologically. Approximately 55% of AML harbour karyotypic changes, and one of the most common chromosomal aberrations is the t(8;21)(q22;q22), which leads to the AML1-ETO fusion protein. Previous studies have found that this fusion protein recruits the N-CoR/mSin3A/HDAC complex, thereby acts as a transcriptional repressor. Recently, DNA methylation array studies have shown that DNA methylation patterns can stratify AML cases into different subgroups, and some of these correspond to certain chromosomal abnormalities, such as the t(8;21). These findings suggest a possible link between the fusion transcript AML1-ETO and epigenetic modifications. Additionally, c-kit mutations have emerged as an important disease modifier in the t(8;21) AML and are correlated with poor overall survival and event free survival in patients with t(8;21) AML. We therefore sought to investigate whether there are different DNA methylation patterns in t(8;21) AML with or without c-kit mutations. In our series, 52.2% of the t(8;21) AMLs harbored c-kit mutations, which were correlated with poor event free survival. We next performed pyrosequencing on a selected panel of genes and pinpointed the THBS4 and PAWR genes as hypermethylated in their promoter CpG islands in 86.4% and 59.1% of the t(8;21) AML patients, respectively. These data suggest that THBS4 and PAWR may be important in the pathogenesis of t(8;21) AML. | - |
dc.language | eng | - |
dc.publisher | The University of Hong Kong (Pokfulam, Hong Kong) | - |
dc.relation.ispartof | HKU Theses Online (HKUTO) | - |
dc.rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.source.uri | http://hub.hku.hk/bib/B47151389 | - |
dc.subject.lcsh | DNA - Methylation. | - |
dc.subject.lcsh | Acute myeloid leukemia - Genetic aspects. | - |
dc.title | DNA methylation patterns in t(8;21) acute myeloid leukemia patients | - |
dc.type | PG_Thesis | - |
dc.identifier.hkul | b4715138 | - |
dc.description.thesisname | Master of Philosophy | - |
dc.description.thesislevel | Master | - |
dc.description.thesisdiscipline | Pathology | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.5353/th_b4715138 | - |
dc.date.hkucongregation | 2012 | - |
dc.identifier.mmsid | 991032816739703414 | - |