DNA hypermethylation of cell cycle (p15 and p16) and apoptotic (p14, p53, DAPK and TMS1) genes in peripheral blood of leukemia patients.

Abstract

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.

• Authors: Khaldon Bodoor, Yazan Haddad, Asem Alkhateeb, Abdullah Al-Abbadi, Mohammad Dowairi, Ahmad Magableh, Nazzal Bsoul, Abdulhameed Ghabkari
• Journal: Asian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 15 Issue 1 Pg. 75-84 ( 2014) ISSN: 2476-762X [Electronic] Thailand
• PMID: 24528084 (Publication Type: Journal Article)

Chemical References

• CARD Signaling Adaptor Proteins
• Cyclin-Dependent Kinase Inhibitor p15
• Cyclin-Dependent Kinase Inhibitor p16
• Cytoskeletal Proteins
• PYCARD protein, human
• Tumor Suppressor Protein p14ARF
• Tumor Suppressor Protein p53
• Death-Associated Protein Kinases

Topics

• Adolescent
• Adult
• Aged
• Apoptosis (genetics)
• CARD Signaling Adaptor Proteins
• Cell Cycle (genetics)
• Child
• Child, Preschool
• Cyclin-Dependent Kinase Inhibitor p15 (genetics)
• Cyclin-Dependent Kinase Inhibitor p16 (genetics)
• Cytoskeletal Proteins (genetics)
• DNA Methylation
• Death-Associated Protein Kinases (genetics)
• Female
• Genes, p16
• Genes, p53
• Humans
• Leukemia (blood, genetics)
• Leukemia, Lymphocytic, Chronic, B-Cell (blood, genetics)
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (blood, genetics)
• Leukemia, Myeloid, Acute (blood, genetics)
• Male
• Middle Aged
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (blood, genetics)
• Tumor Suppressor Protein p14ARF (genetics)
• Tumor Suppressor Protein p53 (genetics)
• Young Adult