Aberrant hydroxymethylation in promoter CpG regions of genes related to the cell cycle and apoptosis characterizes advanced chronic myeloid leukemia disease, poor imatinib respondents and poor survival
Abstract Background There is strong evidence that disease progression, drug response and overall clinical outcomes of CML disease are not only decided by BCR/ABL1 oncoprotein but depend on accumulation of additional genetic and epigenetic aberrations. DNA hydroxymethylation is implicated in the deve...
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-022-09481-9 |
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| author | Sameer Ahmad Guru Mamta Pervin Sumi Abdul Rashid Mir Mirza Masroor Ali Beg Bidhan Chandra koner Alpana Saxena |
| author_facet | Sameer Ahmad Guru Mamta Pervin Sumi Abdul Rashid Mir Mirza Masroor Ali Beg Bidhan Chandra koner Alpana Saxena |
| author_sort | Sameer Ahmad Guru |
| collection | DOAJ |
| description | Abstract Background There is strong evidence that disease progression, drug response and overall clinical outcomes of CML disease are not only decided by BCR/ABL1 oncoprotein but depend on accumulation of additional genetic and epigenetic aberrations. DNA hydroxymethylation is implicated in the development of variety of diseases. DNA hydroxymethylation in gene promoters plays important roles in disease progression, drug response and clinical outcome of various diseases. Therefore in this study, we aimed to explore the role of aberrant hydroxymethylation in promoter regions of different tumor suppressor genes in relation to CML disease progression, response to imatinib therapy and clinical outcome. Methods We recruited 150 CML patients at different clinical stages of the disease. Patients were followed up for 48 months and haematological/molecular responses were analysed. Haematological response was analysed by peripheral blood smear. BCR/ABL1 specific TaqMan probe based qRT-PCR was used for assessing the molecular response of CML patients on imatinib therapy. Promoter hydroxymethylation of the genes was characterized using MS-PCR. Results We observed that promoter hydroxymethylation of DAPK1, RIZ1, P16INK4A, RASSF1A and p14ARFARF genes characterize advanced CML disease and poor imatinib respondents. Although, cytokine signalling (SOCS1) gene was hypermethylated in advanced stages of CML and accumulated in patients with poor imatinib response, but the differences were not statistically significant. Moreover, we found hypermethylation of p14ARF, RASSF1 and p16INK4A genes and cytokine signalling gene (SOCS1) significantly associated with poor overall survival of CML patients on imatinib therapy. The results of this study are in agreement of the role of aberrant DNA methylation of different tumor suppressor genes as potential biomarkers of CML disease progression, poor imatinib response and overall clinical outcome. Conclusion In this study, we report that promoter hydroxymethylation of DAPK1, RIZ1, P16INK4A, RASSF1A and p14ARFARF genes is a characteristic feature of CML disease progressions, defines poor imatinib respondents and poor overall survival of CML patients to imatinib therapy. |
| first_indexed | 2024-04-14T00:59:50Z |
| format | Article |
| id | doaj.art-e5ad63302a24463a8d09a744b6b8bb39 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-14T00:59:50Z |
| publishDate | 2022-04-01 |
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| spelling | doaj.art-e5ad63302a24463a8d09a744b6b8bb392022-12-22T02:21:27ZengBMCBMC Cancer1471-24072022-04-0122111510.1186/s12885-022-09481-9Aberrant hydroxymethylation in promoter CpG regions of genes related to the cell cycle and apoptosis characterizes advanced chronic myeloid leukemia disease, poor imatinib respondents and poor survivalSameer Ahmad Guru0Mamta Pervin Sumi1Abdul Rashid Mir2Mirza Masroor Ali Beg3Bidhan Chandra koner4Alpana Saxena5Lurie Children’s Hospital and Stanley Manne Children’s Research Institute, Northwestern UniversityDepartment of Inflammation and Immunity, Lerner Research Institute, Cleve Land ClinicKingdom of Saudi Arabia, University of TabukFaculty of Medicine and Center for Promotion of Medical Research, Faculty of Medical Sciences, Ala-Too International UniversityDepartment of Biochemistry, Hamdard Institute of Medical Science and Research (HIMSR)Department of Biochemistry, Multidisciplinary Research Unit (MRU), Maulana Azad Medical CollegeAbstract Background There is strong evidence that disease progression, drug response and overall clinical outcomes of CML disease are not only decided by BCR/ABL1 oncoprotein but depend on accumulation of additional genetic and epigenetic aberrations. DNA hydroxymethylation is implicated in the development of variety of diseases. DNA hydroxymethylation in gene promoters plays important roles in disease progression, drug response and clinical outcome of various diseases. Therefore in this study, we aimed to explore the role of aberrant hydroxymethylation in promoter regions of different tumor suppressor genes in relation to CML disease progression, response to imatinib therapy and clinical outcome. Methods We recruited 150 CML patients at different clinical stages of the disease. Patients were followed up for 48 months and haematological/molecular responses were analysed. Haematological response was analysed by peripheral blood smear. BCR/ABL1 specific TaqMan probe based qRT-PCR was used for assessing the molecular response of CML patients on imatinib therapy. Promoter hydroxymethylation of the genes was characterized using MS-PCR. Results We observed that promoter hydroxymethylation of DAPK1, RIZ1, P16INK4A, RASSF1A and p14ARFARF genes characterize advanced CML disease and poor imatinib respondents. Although, cytokine signalling (SOCS1) gene was hypermethylated in advanced stages of CML and accumulated in patients with poor imatinib response, but the differences were not statistically significant. Moreover, we found hypermethylation of p14ARF, RASSF1 and p16INK4A genes and cytokine signalling gene (SOCS1) significantly associated with poor overall survival of CML patients on imatinib therapy. The results of this study are in agreement of the role of aberrant DNA methylation of different tumor suppressor genes as potential biomarkers of CML disease progression, poor imatinib response and overall clinical outcome. Conclusion In this study, we report that promoter hydroxymethylation of DAPK1, RIZ1, P16INK4A, RASSF1A and p14ARFARF genes is a characteristic feature of CML disease progressions, defines poor imatinib respondents and poor overall survival of CML patients to imatinib therapy.https://doi.org/10.1186/s12885-022-09481-9Chronic Myeloid LeukaemiaImatinibEpigeneticsPromoter hypermethylationCell cycle and apoptosis related genes |
| spellingShingle | Sameer Ahmad Guru Mamta Pervin Sumi Abdul Rashid Mir Mirza Masroor Ali Beg Bidhan Chandra koner Alpana Saxena Aberrant hydroxymethylation in promoter CpG regions of genes related to the cell cycle and apoptosis characterizes advanced chronic myeloid leukemia disease, poor imatinib respondents and poor survival BMC Cancer Chronic Myeloid Leukaemia Imatinib Epigenetics Promoter hypermethylation Cell cycle and apoptosis related genes |
| title | Aberrant hydroxymethylation in promoter CpG regions of genes related to the cell cycle and apoptosis characterizes advanced chronic myeloid leukemia disease, poor imatinib respondents and poor survival |
| title_full | Aberrant hydroxymethylation in promoter CpG regions of genes related to the cell cycle and apoptosis characterizes advanced chronic myeloid leukemia disease, poor imatinib respondents and poor survival |
| title_fullStr | Aberrant hydroxymethylation in promoter CpG regions of genes related to the cell cycle and apoptosis characterizes advanced chronic myeloid leukemia disease, poor imatinib respondents and poor survival |
| title_full_unstemmed | Aberrant hydroxymethylation in promoter CpG regions of genes related to the cell cycle and apoptosis characterizes advanced chronic myeloid leukemia disease, poor imatinib respondents and poor survival |
| title_short | Aberrant hydroxymethylation in promoter CpG regions of genes related to the cell cycle and apoptosis characterizes advanced chronic myeloid leukemia disease, poor imatinib respondents and poor survival |
| title_sort | aberrant hydroxymethylation in promoter cpg regions of genes related to the cell cycle and apoptosis characterizes advanced chronic myeloid leukemia disease poor imatinib respondents and poor survival |
| topic | Chronic Myeloid Leukaemia Imatinib Epigenetics Promoter hypermethylation Cell cycle and apoptosis related genes |
| url | https://doi.org/10.1186/s12885-022-09481-9 |
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