Journal
CANCER RESEARCH AND TREATMENT
Volume 49, Issue 3, Pages 790-797Publisher
KOREAN CANCER ASSOCIATION
DOI: 10.4143/crt.2016.108
Keywords
p15(Ink4b); Acute promyelocytic leukemia; Arsenic tri-oxide; Leukocytosis; Promoter hypermethylation; Kashmir
Categories
Funding
- SKIMS administration
Ask authors/readers for more resources
Purpose The p15(Ink4b) gene exerts its influence as an inhibitor of cyclin-dependent kinases and is frequently associated with hematological malignancies. Inactivation of this gene through DNA methylation has been found to be the most prevalent epigenetic alteration reported, with a high frequency in all French-American-British subtypes of acute myeloid leukemias, including acute promyelocytic leukemia (APL). In this study, we investigated the prognostic significance of p15 gene promoter hypermethylation and its expression in APL patients of Kashmir (North India). Materials and Methods p15 gene promoter hypermethylation was conducted by methylation-specific polymerase chain reaction, while its subsequent expression analysis was carried out by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Results Of the 37 patients, 16 (43.2%) were found to have methylated p15 genes. Of these 16 cases, seven (43.8%) were methylated partially and nine (56.2%) were found to have complete methylation. Moreover, nine of the 37 patients (24.3%) who presented with leukocytosis at their baseline had complete p15 gene methylation as well (p < 0.05). Semi quantitative RT-PCR showed a complete loss of p15 expression in nine patients with complete methylation coupled with leukocytosis (p=0.031), while seven patients with partial methylation showed decreased p15 expression. Six patients relapsed during the maintenance phase of treatment and were found to have a completely methylated p15 gene and no p15 mRNA. Conclusion Complete methylation and loss of p15 gene expression causes susceptibility to relapse and decreased survival in APL patients. Thus, p15 promoter hypermethylation is a prospective prognostic indicator and a reliable clinical aid in assessment of patients with APL.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available