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DNA methylation profiles in the human genes for tumor necrosis factors. alpha. and. beta. in subpopulations of leukocytes and in leukemias

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America; (United States)
The genomic sequencing technique has been applied to assess the state of methylation in the DNA from human leukocyte subpopulations from healthy individuals and in the DNA from several individuals with myeloid or lymphatic leukemias or non-Hodgkin lymphomas. Leukocyte populations were purified by the high-gradient magnetic cell sorting technique. In the human tumor necrosis factor {alpha} (TNF-{alpha}) gene segment between nucleotides 300 and 1150, the specific methylation profile in the DNA from human granulocytes and monocytes is maintained in three cases of myeloid leukemia. In the TNF-{beta} gene, DNA methylation is decreased in several examples of acute or chronic myeloid leukemias in comparison to normal human granulocytes or monocytes, whose DNA is almost completely methylated between nucleotides 700 and 900. In human T and B lymphocytes, the main producers of TNF-{beta}, in three instances of chronic lymphatic leukemias and two cases of non-Hodgkin lymphomas, all 5{prime}-CG-3{prime} sequences are unmethylated in this region. The DNA from the human HeLa cell line is highly methylated at all 5{prime}-CG-3{prime} sequences in the TNF-{alpha} and -{beta} genes. The TNF-{alpha} gene is transcribed in the cells of one case of acute myeloid leukemia in which the analyzed region of the TNF-{alpha} gene is completely unmethylated. The TNF-{beta} gene is not transcribed in any of the malignant cells tested.
OSTI ID:
5933493
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:13; ISSN 0027-8424; ISSN PNASA
Country of Publication:
United States
Language:
English