Death associated protein kinase-1 gene methylation pattern in some leukemic patients attending Zagazig University hospitals: is it a clue?

Background: Leukemia is a type of cancer arising from white blood cells (WBCs) and resulting from malignant transformation of different types of white blood cell precursors. The objective was to study the DAPK-1 gene methylation pattern in leukemic patients and to through some light on its possible role as a risk factor for leukemia. Methods: Forty-one patients diagnosed as leukemic patients and 41 age-matched healthy unrelated volunteers taken as a control group. The analysis of aberrant promoter DAPK1 gene methylation was done by specific polymerase chain reaction. Results: The results of the present study showed that there was a significant association of methylated DAPK-1 promoter area among leukemic group than in control group Chi-square (X 2 ) was 21.98, or value patients was 10.46 and there was a significant association when compared with the control group (p <0.001). And there was no significant association when compared according to gender Chi-square (X 2 ) was 0.43 and (p=0.51). Our results revealed in the AML group DAPK-1 promoter area were methylated with percentage of 73.9%. or value for AML patients was 13.76 and there was a significant association when compared with the control group (p <0.001), in the ALL group 4 patients had methylated DAPK-1 promoter area with percentage of 57.1% or value for all patients was 6.47 and there was a significant association when compared with the control group (p=0.03) and in the CLL group 7 patients had methylated DAPK-1 promoter area with percentage of 63.6%. OR value for CCL patients was 8.5 and there was a significant association when compared with the control group (p=0.004). On the contrary, we didn’t observe any significant associations between DAPK-1 promoter area methylation and the type of leukemia (p = 0.65). Conclusions: These results suggested that DAPK1 promoter methylation might play a significant role in the pathogenesis of different types of leukemia. And the DAPK1 promoter methylation has a predictive value in the prediction of leukemia occurrence.

[1]  N. Varol,et al.  Methylation analysis of the DAPK1 gene in imatinib-resistant chronic myeloid leukemia patients , 2014, Oncology letters.

[2]  H. Blom,et al.  Cytosine DNA Methylation Is Found in Drosophila melanogaster but Absent in Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Other Yeast Species , 2014, Analytical chemistry.

[3]  Y. Kwong,et al.  Epigenetic inactivation of mir-34b/c in addition to mir-34a and DAPK1 in chronic lymphocytic leukemia , 2014, Journal of Translational Medicine.

[4]  R. Schneider-Stock,et al.  Transcription control of DAPK , 2013, Apoptosis.

[5]  A. Saxena,et al.  Epigenetic Silencing of DAPK1 Gene is Associated with Faster Disease Progression in India Populations with Chronic Myeloid Leukemia , 2013 .

[6]  J. Byrd,et al.  Germline Allele-Specific Expression of DAPK1 in Chronic Lymphocytic Leukemia , 2013, PloS one.

[7]  Iannis Aifantis,et al.  Mechanisms of epigenetic regulation of leukemia onset and progression. , 2013, Advances in immunology.

[8]  J. Byrd,et al.  Quantitative analyses of DAPK1 methylation in AML and MDS , 2012, International journal of cancer.

[9]  A. Chatterjee,et al.  Methylation of death-associated protein kinase is associated with cetuximab and erlotinib resistance , 2012, Cell cycle.

[10]  H. Choung,et al.  Multigene methylation analysis of ocular adnexal MALT lymphoma and their relationship to Chlamydophila psittaci infection and clinical characteristics in South Korea. , 2012, Investigative ophthalmology & visual science.

[11]  H. Koeffler,et al.  Aberrant methylation in promoter-associated CpG islands of multiple genes in chronic myelogenous leukemia blast crisis. , 2012, Oncology letters.

[12]  A. Órfão,et al.  Immunophenotyping of acute leukemia and lymphoproliferative disorders: a consensus proposal of the European LeukemiaNet Work Package 10 , 2011, Leukemia.

[13]  M. Lacher,et al.  Altered expression of imprinted genes in Wilms tumors. , 2011, Oncology reports.

[14]  K. Jahnukainen,et al.  Response-guided induction therapy in pediatric acute myeloid leukemia with excellent remission rate. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  N. Olgun,et al.  Expression and Methylation Pattern of p16 in Neuroblastoma Tumorigenesis , 2010, Pathology & Oncology Research.

[16]  S. Belinsky,et al.  Dual promoter regulation of death-associated protein kinase gene leads to differentially silenced transcripts by methylation in cancer. , 2009, Carcinogenesis.

[17]  Chris A. Nasrallah,et al.  Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies. , 2009, Blood.

[18]  J. L. Paternáin,et al.  Specific gene hypomethylation and cancer: New insights into coding region feature trends , 2009, Bioinformation.

[19]  M. Copland,et al.  Stem Cells in Leukemia and Other Hematological Malignancies , 2009 .

[20]  J. Lee,et al.  DNA Methylation Profiles of MGMT, DAPK1, hMLH1, CDH1, SHP1, and HIC1 in B-Cell Lymphomas , 2009 .

[21]  H. Ngan,et al.  Promoter methylation of death-associated protein kinase and its role in irradiation response in cervical cancer. , 2008, Oncology reports.

[22]  S. Gygi,et al.  The Tumor Suppressor DAP Kinase Is a Target of RSK-Mediated Survival Signaling , 2005, Current Biology.

[23]  K. Bhatia,et al.  Aberrant methylation of multiple tumor suppressor genes in acute myeloid leukemia , 2004, American journal of hematology.

[24]  K. Bhatia,et al.  Concurrent methylation of multiple genes in childhood ALL: Correlation with phenotype and molecular subgroup , 2003, Leukemia.

[25]  M. Alonso,et al.  CpG island methylation status and mutation analysis of the RB1 gene essential promoter region and protein-binding pocket domain in nervous system tumours , 2003, British Journal of Cancer.

[26]  R. Liang,et al.  Hypermethylation of gene promoters in hematological neoplasia , 2002, Hematological oncology.

[27]  M. Toyota,et al.  DNA methylation and histone deacetylation associated with silencing DAP kinase gene expression in colorectal and gastric cancers , 2002, British Journal of Cancer.

[28]  H. Ng,et al.  Frequent death-associated protein kinase promoter hypermethylation in multiple myeloma. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[29]  A. Reeve,et al.  Epigenetic changes at the insulin-like growth factor II/H19 locus in developing kidney is an early event in Wilms tumorigenesis. , 1997, Proceedings of the National Academy of Sciences of the United States of America.