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- W2334299077 abstract "Elevated expression of Meis1 and Hoxa9 is commonly seen in human leukemia and often indicates a poor prognosis. It has also been shown that overexpression of Meis1 together with Hoxa9 cause acute myeloid leukemia (AML) in mice. However, the molecular mechanisms responsible for the collaboration between Meis1 and Hoxa9 in transformation to AML are not fully understood. DNA methylation is a highly conserved mechanism for the regulation of vital biological processes. Changes in DNA methylation are a common feature of human AML suggesting a role in leukemia development. Furthermore, it has been shown that Meis1 can disrupt DNA methylation and the genomic imprint together with HOX-fusion genes, thus, warranting further investigation. To investigate the effect of overexpression of Meis1 together with Hoxa9 on DNA methylation in bone marrow cells we have established a cell culturing system based on retroviral transduction of murine bone marrow cells. These cells are fully transplantable even after extended time in culture. The cells were cultured for 3 weeks before genomic DNA was isolated. Methylated DNA was enriched (MethylMiner®,Invitrogen) and subjected, in biological duplicates, to a whole genome promoter array (2.1M Mouse Promoter Array, NimbleGen). Data analysis showed high consistency between the duplicate samples. There were approximately 38,000 hypermethylated regions identified in both Hoxa9/Meis1 and Hoxa9 overexpressing cells, indicating no obvious difference in overall DNA methylation between Hoxa9/Meis1 or Hoxa9 cells. However, there was a distinct difference in DNA methylation pattern and approximately 1500 regions were found differentially hypermethylated in Hoxa9/Meis1 cells compared to Hoxa9 cells. These results show that overexpression of Meis1 together with Hoxa9 lead to gain or loss of DNA methylation in distinct regions in the genome but do not seem to lead to a change in the overall degree of methylation. Further investigations of regions are underway and will reveal new insight in Hoxa9/Meis1 induced leukemogenesis." @default.
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- W2334299077 date "2013-08-01" @default.
- W2334299077 modified "2023-10-18" @default.
- W2334299077 title "DNA methylation changes induced by Meis1 in a Hoxa9/Meis1 acute leukemia model" @default.
- W2334299077 doi "https://doi.org/10.1016/j.exphem.2013.05.223" @default.
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