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Aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among north indian population

Aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among north indian population

Promoter hypermethylation mediates gene silencing in many neoplasms. Acute leukemia has been reported to harbor multiple genes aberrantly silenced by hypermethylation. Aim: In present study, we investigated the prevalence of hypermethylation of caspase-8 (CASP8), TMS1 and DAPK genes in correlation w...

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Main Authors: Nikbakht, M., Jha, A.K., Malekzadeh, K., Askari, M., Mohammadi, S., Marwaha, R.K., Kaul, D., Kaur, J.
Format: Article
Language:English
Published: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2017
Series:Experimental Oncology
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Original contributions
Online Access:http://dspace.nbuv.gov.ua/handle/123456789/137619
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spelling irk-123456789-1376192018-06-18T03:06:02Z Aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among north indian population Nikbakht, M. Jha, A.K. Malekzadeh, K. Askari, M. Mohammadi, S. Marwaha, R.K. Kaul, D. Kaur, J. Original contributions Promoter hypermethylation mediates gene silencing in many neoplasms. Acute leukemia has been reported to harbor multiple genes aberrantly silenced by hypermethylation. Aim: In present study, we investigated the prevalence of hypermethylation of caspase-8 (CASP8), TMS1 and DAPK genes in correlation with clinicopathological factors in childhood acute lymphoblastic leukemia (ALL). Materials and Methods: A case-control study has been conducted based on bone marrow and peripheral blood samples from 125 ALL patients and 100 sex-age matched healthy controls. Methylation specific polymerase chain reaction (PCR) and bisulfite sequencing PCR was performed to analyze the methylation status of these genes. Reverse transcription PCR and real time PCR was carried out to determine changes in the mRNA expression level of the genes due to hypermethylation. Results: Hypermethylation of the 5´CpG islands of the CASP8, TMS1 and DAPK gene promoters was found in 3.2, 6.4, and 13.6% of 125 childhood ALL samples from north Indian population, respectively. There were significant differences in pattern of hypermethylation of TMS1 (p = 0.045) and DAPK (p < 0.001) between patients and healthy controls. Down-regulation of mRNA expression was found in cases in which CASP8, TMS1 and DAPK were hypermethylated. Conclusions: The present study indicated the impact of hypermethylation-mediated inactivation of CASP8, TMS1 and DAPK genes, which is associated with risk of childhood ALL. This abnormality occurs in leukemogenesis and it may be used as a biomarker and for predicting the prognosis of ALL. 2017 Article Aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among north indian population / M. Nikbakht, A.K. Jha, K. Malekzadeh, M. Askari, S. Mohammadi, R.K. Marwaha, D. Kaul, J. Kaur // Experimental Oncology. — 2017 — Т. 39, № 1. — С. 57-64. — Бібліогр.: 51 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/137619 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
collection DSpace DC
language English
topic Original contributions
Original contributions
spellingShingle Original contributions
Original contributions
Nikbakht, M.
Jha, A.K.
Malekzadeh, K.
Askari, M.
Mohammadi, S.
Marwaha, R.K.
Kaul, D.
Kaur, J.
Aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among north indian population
Experimental Oncology
description Promoter hypermethylation mediates gene silencing in many neoplasms. Acute leukemia has been reported to harbor multiple genes aberrantly silenced by hypermethylation. Aim: In present study, we investigated the prevalence of hypermethylation of caspase-8 (CASP8), TMS1 and DAPK genes in correlation with clinicopathological factors in childhood acute lymphoblastic leukemia (ALL). Materials and Methods: A case-control study has been conducted based on bone marrow and peripheral blood samples from 125 ALL patients and 100 sex-age matched healthy controls. Methylation specific polymerase chain reaction (PCR) and bisulfite sequencing PCR was performed to analyze the methylation status of these genes. Reverse transcription PCR and real time PCR was carried out to determine changes in the mRNA expression level of the genes due to hypermethylation. Results: Hypermethylation of the 5´CpG islands of the CASP8, TMS1 and DAPK gene promoters was found in 3.2, 6.4, and 13.6% of 125 childhood ALL samples from north Indian population, respectively. There were significant differences in pattern of hypermethylation of TMS1 (p = 0.045) and DAPK (p < 0.001) between patients and healthy controls. Down-regulation of mRNA expression was found in cases in which CASP8, TMS1 and DAPK were hypermethylated. Conclusions: The present study indicated the impact of hypermethylation-mediated inactivation of CASP8, TMS1 and DAPK genes, which is associated with risk of childhood ALL. This abnormality occurs in leukemogenesis and it may be used as a biomarker and for predicting the prognosis of ALL.
format Article
author Nikbakht, M.
Jha, A.K.
Malekzadeh, K.
Askari, M.
Mohammadi, S.
Marwaha, R.K.
Kaul, D.
Kaur, J.
author_facet Nikbakht, M.
Jha, A.K.
Malekzadeh, K.
Askari, M.
Mohammadi, S.
Marwaha, R.K.
Kaul, D.
Kaur, J.
author_sort Nikbakht, M.
title Aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among north indian population
title_short Aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among north indian population
title_full Aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among north indian population
title_fullStr Aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among north indian population
title_full_unstemmed Aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among north indian population
title_sort aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among north indian population
publisher Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
publishDate 2017
topic_facet Original contributions
url http://dspace.nbuv.gov.ua/handle/123456789/137619
citation_txt Aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among north indian population / M. Nikbakht, A.K. Jha, K. Malekzadeh, M. Askari, S. Mohammadi, R.K. Marwaha, D. Kaul, J. Kaur // Experimental Oncology. — 2017 — Т. 39, № 1. — С. 57-64. — Бібліогр.: 51 назв. — англ.
series Experimental Oncology
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first_indexed 2023-10-18T21:16:09Z
last_indexed 2023-10-18T21:16:09Z
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