TY - JOUR
T1 - The estrogen receptor CpG island is methylated in most hematopoietic neoplasms
AU - Issa, Jean Pierre J.
AU - Zehnbauer, Barbara A.
AU - Civin, Curt I.
AU - Collector, Michael
AU - Sharkis, Saul J
AU - Davidson, Nancy E.
AU - Kaufmann, Scott H.
AU - Baylin, Stephen B.
PY - 1996/3/1
Y1 - 1996/3/1
N2 - 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.
AB - 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.
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M3 - Article
C2 - 8640788
AN - SCOPUS:0030063853
SN - 0008-5472
VL - 56
SP - 973
EP - 977
JO - Cancer Research
JF - Cancer Research
IS - 5
ER -