DOK6 promoter methylation serves as a potential biomarker affecting prognosis in de novo acute myeloid leukemia
Abstract Background Downstream of tyrosine kinase 6 (DOK6), which is specifically expressed in the nervous system, was previously recognized as an adapter only in neurite outgrowth. Recent studies also demonstrated the potential role of DOK6 in solid tumors such as gastric cancer and breast cancer....
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-10-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.2540 |
| _version_ | 1828397689066225664 |
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| author | Guo‐Kang Sun Li‐Juan Tang Jing‐Dong Zhou Zi‐Jun Xu Lan Yang Qian Yuan Ji‐Chun Ma Xing‐Hui Liu Jiang Lin Jun Qian Dong‐Ming Yao |
| author_facet | Guo‐Kang Sun Li‐Juan Tang Jing‐Dong Zhou Zi‐Jun Xu Lan Yang Qian Yuan Ji‐Chun Ma Xing‐Hui Liu Jiang Lin Jun Qian Dong‐Ming Yao |
| author_sort | Guo‐Kang Sun |
| collection | DOAJ |
| description | Abstract Background Downstream of tyrosine kinase 6 (DOK6), which is specifically expressed in the nervous system, was previously recognized as an adapter only in neurite outgrowth. Recent studies also demonstrated the potential role of DOK6 in solid tumors such as gastric cancer and breast cancer. However, previous studies of DOK6 have not dealt with its roles in myeloid malignancies. Herein, we verified the promoter methylation status of DOK6 and further explored its clinical implication in de novo acute myeloid leukemia (AML). Methods A total of 100 newly diagnosed adult AML patients were involved in the current study. DOK6 expression and methylation were detected by real‐time qPCR and methylation‐specific PCR (MSP), respectively. Bisulfite sequencing PCR (BSP) was performed to assess the methylation density of the DOK6 promoter. Results Downstream of tyrosine kinase 6 promoter methylation was significantly increased in AML patients compared to controls (P = .037), whereas DOK6 expression significantly decreased in AML patients (P < .001). The expression of DOK6 was markedly up‐regulated after treated by 5‐aza‐2′‐deoxycytidine (5‐aza‐dC) in THP‐1 cell lines. The methylation status of the DOK6 promoter was associated with French‐American‐British classifications (P = .037). There was no significant correlation existed between DOK6 expression and its promoter methylation (R = .077, P = .635). Interestingly, of whole‐AML and non‐APL AML patients, both have a tendency pertaining to the DOK6 methylation group and a significantly longer overall survival (OS) than the DOK6 unmethylation group (P = .042 and .036, respectively). Conclusion Our study suggested that DOK6 promoter hypermethylation was a common molecular event in de novo AML patients. Remarkably, DOK6 promoter methylation could serve as an independent and integrated prognostic biomarker not only in non‐APL AML patients but also in AML patients who are less than 60 years old. |
| first_indexed | 2024-12-10T08:52:02Z |
| format | Article |
| id | doaj.art-a4e6d0fba603476c86011a6f3b4f375a |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-12-10T08:52:02Z |
| publishDate | 2019-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-a4e6d0fba603476c86011a6f3b4f375a2022-12-22T01:55:34ZengWileyCancer Medicine2045-76342019-10-018146393640210.1002/cam4.2540DOK6 promoter methylation serves as a potential biomarker affecting prognosis in de novo acute myeloid leukemiaGuo‐Kang Sun0Li‐Juan Tang1Jing‐Dong Zhou2Zi‐Jun Xu3Lan Yang4Qian Yuan5Ji‐Chun Ma6Xing‐Hui Liu7Jiang Lin8Jun Qian9Dong‐Ming Yao10Laboratory Center Affiliated People's Hospital of Jiangsu University Zhenjiang Jiangsu People's Republic of ChinaLaboratory Center Affiliated People's Hospital of Jiangsu University Zhenjiang Jiangsu People's Republic of ChinaLaboratory Center Affiliated People's Hospital of Jiangsu University Zhenjiang Jiangsu People's Republic of ChinaLaboratory Center Affiliated People's Hospital of Jiangsu University Zhenjiang Jiangsu People's Republic of ChinaLaboratory Center Affiliated People's Hospital of Jiangsu University Zhenjiang Jiangsu People's Republic of ChinaThe Key Lab of Precision Diagnosis and Treatment of Zhenjiang City Zhenjiang Jiangsu People's Republic of ChinaThe Key Lab of Precision Diagnosis and Treatment of Zhenjiang City Zhenjiang Jiangsu People's Republic of ChinaDepartment of Clinical Laboratory Shanghai Gongli Hospital The Second Military Medical University Shanghai ChinaThe Key Lab of Precision Diagnosis and Treatment of Zhenjiang City Zhenjiang Jiangsu People's Republic of ChinaThe Key Lab of Precision Diagnosis and Treatment of Zhenjiang City Zhenjiang Jiangsu People's Republic of ChinaLaboratory Center Affiliated People's Hospital of Jiangsu University Zhenjiang Jiangsu People's Republic of ChinaAbstract Background Downstream of tyrosine kinase 6 (DOK6), which is specifically expressed in the nervous system, was previously recognized as an adapter only in neurite outgrowth. Recent studies also demonstrated the potential role of DOK6 in solid tumors such as gastric cancer and breast cancer. However, previous studies of DOK6 have not dealt with its roles in myeloid malignancies. Herein, we verified the promoter methylation status of DOK6 and further explored its clinical implication in de novo acute myeloid leukemia (AML). Methods A total of 100 newly diagnosed adult AML patients were involved in the current study. DOK6 expression and methylation were detected by real‐time qPCR and methylation‐specific PCR (MSP), respectively. Bisulfite sequencing PCR (BSP) was performed to assess the methylation density of the DOK6 promoter. Results Downstream of tyrosine kinase 6 promoter methylation was significantly increased in AML patients compared to controls (P = .037), whereas DOK6 expression significantly decreased in AML patients (P < .001). The expression of DOK6 was markedly up‐regulated after treated by 5‐aza‐2′‐deoxycytidine (5‐aza‐dC) in THP‐1 cell lines. The methylation status of the DOK6 promoter was associated with French‐American‐British classifications (P = .037). There was no significant correlation existed between DOK6 expression and its promoter methylation (R = .077, P = .635). Interestingly, of whole‐AML and non‐APL AML patients, both have a tendency pertaining to the DOK6 methylation group and a significantly longer overall survival (OS) than the DOK6 unmethylation group (P = .042 and .036, respectively). Conclusion Our study suggested that DOK6 promoter hypermethylation was a common molecular event in de novo AML patients. Remarkably, DOK6 promoter methylation could serve as an independent and integrated prognostic biomarker not only in non‐APL AML patients but also in AML patients who are less than 60 years old.https://doi.org/10.1002/cam4.2540AMLbiomarkerDOK6methylationprognosis |
| spellingShingle | Guo‐Kang Sun Li‐Juan Tang Jing‐Dong Zhou Zi‐Jun Xu Lan Yang Qian Yuan Ji‐Chun Ma Xing‐Hui Liu Jiang Lin Jun Qian Dong‐Ming Yao DOK6 promoter methylation serves as a potential biomarker affecting prognosis in de novo acute myeloid leukemia Cancer Medicine AML biomarker DOK6 methylation prognosis |
| title | DOK6 promoter methylation serves as a potential biomarker affecting prognosis in de novo acute myeloid leukemia |
| title_full | DOK6 promoter methylation serves as a potential biomarker affecting prognosis in de novo acute myeloid leukemia |
| title_fullStr | DOK6 promoter methylation serves as a potential biomarker affecting prognosis in de novo acute myeloid leukemia |
| title_full_unstemmed | DOK6 promoter methylation serves as a potential biomarker affecting prognosis in de novo acute myeloid leukemia |
| title_short | DOK6 promoter methylation serves as a potential biomarker affecting prognosis in de novo acute myeloid leukemia |
| title_sort | dok6 promoter methylation serves as a potential biomarker affecting prognosis in de novo acute myeloid leukemia |
| topic | AML biomarker DOK6 methylation prognosis |
| url | https://doi.org/10.1002/cam4.2540 |
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