THE ESTROGEN-RECEPTOR CPG ISLAND IS METHYLATED IN MOST HEMATOPOIETIC NEOPLASMS

Estrogen appears to be a negative regulator of normal hematopoiesis. C hromosome 6q, which contains the estrogen receptor (ER) gene, is frequ ently altered in human hematopoietic neoplasms. The ER gene, which has growth and metastasis suppressor activity in many different cell type s, is inactivated by promoter methylation in some ER-negative breast t umors and 100% of colorectal tumors. We now report that the promoter r egion of the ER gene is aberrantly methylated in 86% of human hematopo ietic tumors, including 8 of 9 pediatric acute lymphocytic leukemia, 1 7 of 18 adult acute lymphocytic leukemia, 21 of 23 adult acute myeloge nous leukemia, 3 of 6 chronic phase chronic myelogenous leukemia, 9 of 9 blast crisis chronic myelogenous leukemia and 5 of 8 lymphomas. Thi s methylation event was also present in all nine Leukemia cell lines e xamined, where it was associated with very low or absent ER expression . In addition, rat and mouse leukemia cell lines also exhibited this c hange, indicating that ER CpG island methylation in leukemias is conse rved among species. Our results suggest that ER CpG island methylation could be an important step in the genesis of human hematopoietic neop lasms and might be a useful molecular marker for monitoring the clinic al status of these diseases.