Preferential hypermethylation of the Dickkopf-1 promoter in core-binding factor leukaemia
| Autor: | Makoto Onizuka, Satomi Fukagawa, Ayumi Shintani, Tomomitsu Hotta, Kiyoshi Ando, Hiroshi Kawada, Hiroyuki Kobayashi, Yoshiaki Ogawa, Kosuke Tsuboi, Rikio Suzuki, Masako Shimada, Minoru Kojima |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male musculoskeletal diseases medicine.medical_specialty Adolescent Bone Marrow Cells Biology Core binding factor Gene product hemic and lymphatic diseases Internal medicine Biomarkers Tumor Tumor Cells Cultured medicine Humans Gene silencing Promoter Regions Genetic Aged Aged 80 and over Hematology Reverse Transcriptase Polymerase Chain Reaction Core Binding Factors Wnt signaling pathway DNA Neoplasm Methylation DNA Methylation Middle Aged Precursor Cell Lymphoblastic Leukemia-Lymphoma Prognosis Survival Analysis Neoplasm Proteins DKK1 Leukemia Myeloid Acute Disease DNA methylation Disease Progression Cancer research Intercellular Signaling Peptides and Proteins Female |
| Zdroj: | British Journal of Haematology. 138:624-631 |
| ISSN: | 1365-2141 0007-1048 |
| DOI: | 10.1111/j.1365-2141.2007.06702.x |
| Popis: | The Dickkopf-1 (DKK1) gene product is an extracellular Wnt inhibitor. Hypermethylation of the DKK1 promoter results in transcriptional silencing and may play an important role in cancer development. Here, we investigated hypermethylation of the DKK1 promoter in patients with acute myeloid leukaemia (AML), especially core-binding factor (CBF) leukaemia. The methylation status of DKK1 was analysed using methylation-specific polymerase chain reaction in 47 patients with AML. DKK1 methylation was found in 14 (29.8%) patients, and more frequently in those with CBF leukaemia (6 of 12 patients), than in those with acute promyelocytic leukaemia (APL) (0 of 6 patients) (P = 0.03). In contrast, Wnt inhibitory factor-1 methylation was found in APL (4 of 6 patients) but not in CBF leukaemia (0 of 12 patients) (P = 0.001). Multivariate analyses suggested that DKK1 methylation was a risk factor for poorer overall survival. Sequential analysis using four paired samples obtained at diagnosis and relapse suggested that DKK1 methylation was involved in the progression of leukaemia. Therefore, DKK1 methylation may be involved in leukaemogenesis, especially in CBF leukaemia, and may be a useful prognostic marker in AML. |
| Databáze: | OpenAIRE |
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