Epigenetic dysregulation of the DAP kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in acute leukaemias

Chim, Chor Sang; Chan, Wai-Sun; Kwong, Yok Lam

doi:10.1136/jcp.2007.047324

Cited by 11 publications

(14 citation statements)

References 36 publications

(27 reference statements)

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“…As for the AML patients, only one out of 12 cases displayed methylation in this gene. Chim et al (2008) and Christiansen et al (2003) reported absence of p14 methylation in AML patients, which was consistent with RNA expression studies (Schwaller et al, 1997). On the other hand, five CLL patients out of 20 showed methylation in p14.…”

Section: Discussionsupporting

confidence: 77%

“…Low frequency of DAPK methylation in AML was previously reported (Katzenellenbogen et al, 1999;Galm et al, 2005;Chim et al, 2008;Griffiths et al, 2010). In contrast, Ekmekci et al (2004) reported methylation in 61% of AML patients.…”

Section: Dna Hypermethylation Of Cell Cycle and Apoptotic Genes In Pementioning

confidence: 75%

“…Kusy et al (2003) reported p14 methylation only in one CML patient out of 76, whereas Roman-gomez et al (2004,2006) reported low frequency of methylation in ALL. On the other hand, three reports showed absence of p14 methylation in ALL (Matsushita et al, 2004;Chim et al, 2008;Takeuchi et al, 2012). As for the AML patients, only one out of 12 cases displayed methylation in this gene.…”

Section: Discussionmentioning

confidence: 99%

“…Methylation in p14 gene is absent in AML patients (Christiansen et al, 2003;Chim et al, 2008). Relatively low frequency of methylation was reported in p16 gene (Wong et al, 2000;Chim et al, 2001;Garcia-Manero et al, 2003;Matsushita et al, 2004;Roman-Gomez et al, 2004;Roman-Gomez et al, 2006) and DAPK (Katzenellenbogen et al, 1999;Galm et al, 2005;Chim et al, 2008;Griffiths et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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DNA Hypermethylation of Cell Cycle (p15 and p16) and Apoptotic (p14, p53, DAPK and TMS1) Genes in Peripheral Blood of Leukemia Patients

Bodoor

Haddad

Alkhateeb

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Aberrant DNA methylation of tumor suppressor genes has been reported in all major types of leukemia with potential involvement in the inactivation of regulatory cell cycle and apoptosis genes. However, most of the previous reports did not show the extent of concurrent methylation of multiple genes in the four leukemia types. Here, we analyzed six key genes (p14, p15, p16, p53, DAPK and TMS1) for DNA methylation using methylation specific PCR to analyze peripheral blood of 78 leukemia patients (24 CML, 25 CLL, 12 AML, and 17 ALL) and 24 healthy volunteers. In CML, methylation was detected for p15 (11%), p16 (9%), p53 (23%) and DAPK (23%), in CLL, p14 (25%), p15 (19%), p16 (12%), p53 (17%) and DAPK (36%), in AML, p14 (8%), p15 (45%), p53 (9%) and DAPK (17%) and in ALL, p15 (14%), p16 (8%), and p53 (8%). This study highlighted an essential role of DAPK methylation in chronic leukemia in contrast to p15 methylation in the acute cases, whereas TMS1 hypermethylation was absent in all cases. Furthermore, hypermethylation of multiple genes per patient was observed, with obvious selectiveness in the 9p21 chromosomal region genes (p14, p15 and p16). Interestingly, methylation of p15 increased the risk of methylation in p53, and vice versa, by five folds (p=0.03) indicating possible synergistic epigenetic disruption of different phases of the cell cycle or between the cell cycle and apoptosis. The investigation of multiple relationships between methylated genes might shed light on tumor specific inactivation of the cell cycle and apoptotic pathways.

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Section: Discussionsupporting

confidence: 77%

Section: Dna Hypermethylation Of Cell Cycle and Apoptotic Genes In Pementioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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DNA Hypermethylation of Cell Cycle (p15 and p16) and Apoptotic (p14, p53, DAPK and TMS1) Genes in Peripheral Blood of Leukemia Patients

Bodoor

Haddad

Alkhateeb

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…7,11 The mechanism by which FAS promoter is overmethylated in sAML is still unclear. However, the 5 0 -CpG1-8 are located immediately downstream of the docking site of Dnmt1, which promotes FAS promoter methylation in KRAS-transformed NIH3T3 cells.…”

Section: Letters To the Editormentioning

confidence: 99%

Fas expression at diagnosis as a biomarker of azacitidine activity in high-risk MDS and secondary AML

et al. 2012

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Promoter Hypermethylation as a Biomarker in Prostate Adenocarcinoma

Park

2014

Methods in Molecular Biology

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There is increasing evidence that DNA methylation is a critical source of gene regulation. In addition, interindividual differences in DNA methylation status in cancer related genes are associated with risk and progression of prostate cancer. Therefore, DNA methylation in cancer related genes can be potential biomarkers and therapeutic targets for prostate cancer.In this chapter, current information on frequently hypermethylated genes associated with the carcinogenesis and progression of prostate cancer was updated. The potential biological role of hypermethylated genes in prostate cancer is discussed. These findings may provide new information of the pathogenesis, the exciting potential to be predictive and to provide strategies for personalized treatment of prostate cancer.

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Epigenetic dysregulation of the DAP kinase/p14/HDM2/p53/Apaf-1 apoptosis pathway in acute leukaemias

Abstract: Among AML subtypes, DAP kinase is preferentially hypermethylated in APL.

Cited by 11 publications

References 36 publications

DNA Hypermethylation of Cell Cycle (p15 and p16) and Apoptotic (p14, p53, DAPK and TMS1) Genes in Peripheral Blood of Leukemia Patients

DNA Hypermethylation of Cell Cycle (p15 and p16) and Apoptotic (p14, p53, DAPK and TMS1) Genes in Peripheral Blood of Leukemia Patients

Fas expression at diagnosis as a biomarker of azacitidine activity in high-risk MDS and secondary AML

Promoter Hypermethylation as a Biomarker in Prostate Adenocarcinoma

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