p15Ink4b Loss of Expression by Promoter Hypermethylation Adds to Leukemogenesis and Confers a Poor Prognosis in Acute Promyelocytic Leukemia Patients

Shahid M. Baba; Niyaz A. Azad; Zafar A. Shah; Dil-Afroze; Arshad A. Pandith; Aleem Jan; Sheikh A. Aziz

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자료유형: 학술저널

저자정보: Shahid M. Baba (Sher-I-Kashmir Institute of Medical Sciences India) Niyaz A. Azad (Sher-I-Kashmir Institute of Medical Sciences India) Zafar A. Shah (Sher-I-Kashmir Institute of Medical Sciences India) Dil-Afroze (Sher-I-Kashmir Institute of Medical Sciences India) Arshad A. Pandith (Sher-I-Kashmir Institute of Medical Sciences India) Aleem Jan (Sher-I-Kashmir Institute of Medical Sciences India) Sheikh A. Aziz (Sher-I-Kashmir Institute of Medical Sciences India)

저널정보: 대한암학회 Cancer Research and Treatment Cancer Research and Treatment 제49권 제3호

발행연도: 2017.7

수록면: 790 - 797 (8page)

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Purpose The p15Ink4b 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). Semiquantitative 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.

#p15Ink4b #Acute promyelocytic leukemia #Arsenic tri-oxide #Leukocytosis #Promoter hypermethylation #Kashmir

참고문헌 (22)

참고문헌 신청

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Nobori T / 1994 / Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers / Nature 368:753~756

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