Promoter Hypermethylation of ATG16L2, TFAP2A, EBF2, Calcitonin, ABL1 Kinase Domain T315I Mutation Association with Imatinib Therapy Resistance and Median Survival in CML Patients of North-East India
Background and Objectives: Chronic myeloid leukemia (CML) initiation and progression is regulated by epigenetic and genetic alterations. Imatinib therapy resistance in CML patients is important clinical issue. To understand association of kinase domain mutation and promoter hypermethylation of genes...
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| Format: | Article |
| Language: | English |
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West Asia Organization for Cancer Prevention
2023-02-01
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| Series: | Asian Pacific Journal of Cancer Care |
| Subjects: | |
| Online Access: | http://www.waocp.com/journal/index.php/apjcc/article/view/967 |
| _version_ | 1827370908818341888 |
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| author | Anupam Sarma Amal Chandra Kataki Avdhesh Kumar Rai Munlima Hazarika Partha Sarathi Roy Manoj Kalita Manab Deka Indranil Chattopadhyay |
| author_facet | Anupam Sarma Amal Chandra Kataki Avdhesh Kumar Rai Munlima Hazarika Partha Sarathi Roy Manoj Kalita Manab Deka Indranil Chattopadhyay |
| author_sort | Anupam Sarma |
| collection | DOAJ |
| description | Background and Objectives: Chronic myeloid leukemia (CML) initiation and progression is regulated by epigenetic and genetic alterations. Imatinib therapy resistance in CML patients is important clinical issue. To understand association of kinase domain mutation and promoter hypermethylation of genes with imatinib therapy resistance hold significance in CML patients of North-East India. This study is a hospital based cross sectional study.
Methods: A total of Sixty three (n=63) CML patients undergone imatinib mesylate were enrolled for the study. ABL kinase domain T315I mutation was analyzed by Allele specific- PCR (AS-PCR) and confirmed by sequencing. Promoter hypermethylation was analyzed by Methylation specific PCR (MS-PCR). The Chi square test and Fisher exact test used in SPSS ver19.
Results: Tyrosine Kinase domain mutation T315I was found in 30.1% (19/63). The promoter hypermethylation of Calcitonin, ATG16L2, TFAP2A, EBF2 gene was detected in 42.9% (n=27), 28.6% (n=18), 38.1% (n=24), 27% (n= 17) CML patients respectively. Median relapse free survival was 21 months and statistically significant for CML patients without T315I mutation compared to patients with T315I mutation who has 12 months median relapse free survival (p=0.005). Median survival was 19 months for patients without EBF2 promoter hypermethylation and also statistically significant compared to CML patients with promoter hypermethylation (12 months) (p=0.026).
Interpretation and Conclusions: We conclude that among imatinib resistant CML patients of North- East India harbouring T315I mutation of ABL1 Kinase domain and promoter hypermethylation of EBF2 gene have significantly lower median relapse free survival. |
| first_indexed | 2024-03-08T10:30:28Z |
| format | Article |
| id | doaj.art-67ede0c1b31042dbb145137ea02d4d22 |
| institution | Directory Open Access Journal |
| issn | 2588-3682 |
| language | English |
| last_indexed | 2024-03-08T10:30:28Z |
| publishDate | 2023-02-01 |
| publisher | West Asia Organization for Cancer Prevention |
| record_format | Article |
| series | Asian Pacific Journal of Cancer Care |
| spelling | doaj.art-67ede0c1b31042dbb145137ea02d4d222024-01-27T06:37:59ZengWest Asia Organization for Cancer PreventionAsian Pacific Journal of Cancer Care2588-36822023-02-0181354210.31557/apjcc.2023.8.1.35-42967Promoter Hypermethylation of ATG16L2, TFAP2A, EBF2, Calcitonin, ABL1 Kinase Domain T315I Mutation Association with Imatinib Therapy Resistance and Median Survival in CML Patients of North-East IndiaAnupam Sarma0Amal Chandra Kataki1Avdhesh Kumar Rai2Munlima Hazarika3Partha Sarathi Roy4Manoj Kalita5Manab Deka6Indranil Chattopadhyay7Department of Pathology, Dr B. Borooah Cancer Institute, Guwahati-7810116, Assam, India.Dr B. Borooah Cancer Institute, Guwahati-781016, Assam, India.DBT Centre for Molecular Biology & Cancer Research, Dr B. Borooah Cancer Institute, Guwahati-781016, Assam, India.Department of Medical Oncology, Dr B. Borooah Cancer Institute, Guwahati-781016, Assam, India.Department of Medical Oncology, Dr B. Borooah Cancer Institute, Guwahati-781016, Assam, India.Gauhati University Institute of Science & Technology, Gauhati University, Guwahati-781024, Assam, India.Gauhati University Institute of Science & Technology, Gauhati University, Guwahati-781024, Assam, India.Department of Life Sciences, Central University of Tamil Nadu, Thiruvarur, Tamil Nadu, India.Background and Objectives: Chronic myeloid leukemia (CML) initiation and progression is regulated by epigenetic and genetic alterations. Imatinib therapy resistance in CML patients is important clinical issue. To understand association of kinase domain mutation and promoter hypermethylation of genes with imatinib therapy resistance hold significance in CML patients of North-East India. This study is a hospital based cross sectional study. Methods: A total of Sixty three (n=63) CML patients undergone imatinib mesylate were enrolled for the study. ABL kinase domain T315I mutation was analyzed by Allele specific- PCR (AS-PCR) and confirmed by sequencing. Promoter hypermethylation was analyzed by Methylation specific PCR (MS-PCR). The Chi square test and Fisher exact test used in SPSS ver19. Results: Tyrosine Kinase domain mutation T315I was found in 30.1% (19/63). The promoter hypermethylation of Calcitonin, ATG16L2, TFAP2A, EBF2 gene was detected in 42.9% (n=27), 28.6% (n=18), 38.1% (n=24), 27% (n= 17) CML patients respectively. Median relapse free survival was 21 months and statistically significant for CML patients without T315I mutation compared to patients with T315I mutation who has 12 months median relapse free survival (p=0.005). Median survival was 19 months for patients without EBF2 promoter hypermethylation and also statistically significant compared to CML patients with promoter hypermethylation (12 months) (p=0.026). Interpretation and Conclusions: We conclude that among imatinib resistant CML patients of North- East India harbouring T315I mutation of ABL1 Kinase domain and promoter hypermethylation of EBF2 gene have significantly lower median relapse free survival.http://www.waocp.com/journal/index.php/apjcc/article/view/967chronic myeloid leukemia, t315i mutation, promoter hypermethylation, imatinib mesylate, median survival, north-east india |
| spellingShingle | Anupam Sarma Amal Chandra Kataki Avdhesh Kumar Rai Munlima Hazarika Partha Sarathi Roy Manoj Kalita Manab Deka Indranil Chattopadhyay Promoter Hypermethylation of ATG16L2, TFAP2A, EBF2, Calcitonin, ABL1 Kinase Domain T315I Mutation Association with Imatinib Therapy Resistance and Median Survival in CML Patients of North-East India Asian Pacific Journal of Cancer Care chronic myeloid leukemia, t315i mutation, promoter hypermethylation, imatinib mesylate, median survival, north-east india |
| title | Promoter Hypermethylation of ATG16L2, TFAP2A, EBF2, Calcitonin, ABL1 Kinase Domain T315I Mutation Association with Imatinib Therapy Resistance and Median Survival in CML Patients of North-East India |
| title_full | Promoter Hypermethylation of ATG16L2, TFAP2A, EBF2, Calcitonin, ABL1 Kinase Domain T315I Mutation Association with Imatinib Therapy Resistance and Median Survival in CML Patients of North-East India |
| title_fullStr | Promoter Hypermethylation of ATG16L2, TFAP2A, EBF2, Calcitonin, ABL1 Kinase Domain T315I Mutation Association with Imatinib Therapy Resistance and Median Survival in CML Patients of North-East India |
| title_full_unstemmed | Promoter Hypermethylation of ATG16L2, TFAP2A, EBF2, Calcitonin, ABL1 Kinase Domain T315I Mutation Association with Imatinib Therapy Resistance and Median Survival in CML Patients of North-East India |
| title_short | Promoter Hypermethylation of ATG16L2, TFAP2A, EBF2, Calcitonin, ABL1 Kinase Domain T315I Mutation Association with Imatinib Therapy Resistance and Median Survival in CML Patients of North-East India |
| title_sort | promoter hypermethylation of atg16l2 tfap2a ebf2 calcitonin abl1 kinase domain t315i mutation association with imatinib therapy resistance and median survival in cml patients of north east india |
| topic | chronic myeloid leukemia, t315i mutation, promoter hypermethylation, imatinib mesylate, median survival, north-east india |
| url | http://www.waocp.com/journal/index.php/apjcc/article/view/967 |
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