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The Oncology Center and Departments of Pediatrics [C. I. C.] and Medicine [S. B. B.], The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231
Estrogen appears to be a negative regulator of normal hematopoiesis, Chromosome 6q, which contains the estrogen receptor (ER) gene, is frequently altered in human hematopoietic neoplasms. The ER gene, which has growth and metastasis suppressor activity in many different cell types, is inactivated by promoter methylation in some ER-negative breast tumors and 100% of colorectal tumors. We now report that the promoter region of the ER gene is aberrantly methylated in 86% of human hematopoietic tumors, including 8 of 9 pediatric acute lymphocytic leukemia, 17 of 18 adult acute lymphocytic leukemia, 21 of 23 adult acute myelogenous leukemia, 3 of 6 chronic phase chronic myelogenous leukemia, 9 of 9 blast crisis chronic myelogenous leukemia and 5 of 8 lymphomas. This methylation event was also present in all nine leukemia cell lines examined, where it was associated with very low or absent ER expression. In addition, rat and mouse leukemia cell lines also exhibited this change, indicating that ER CPG island methylation in leukemias is conserved among species. Our results suggest that ER CpG island methylation could be an important step in the genesis of human hematopoietic neoplasms and might be a useful molecular marker for monitoring the clinical status of these diseases.
1 This work was supported by a Young Investigator Award from the American Society of Clinical Oncology (to J-P. J. I.), as well as American Cancer Society Grant IRG1134 and NIH Grant 5RO1CA43318. S. H. K. is a Scholar of the Leukemia Society of America.
2 To whom requests for reprints should be addressed, at The Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231.
3 Present address: Washington University, Pediatric Genetics, Box 8116, 1 Children's Place, St. Louis, MO 63110.
4 Present address: Mayo Clinic, 1301 Guggenheim, 200 First Street SW, Rochester, MN 55905.
Received 12/19/95. Accepted 1/17/96.
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