期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：11
页码：6694-6699
DOI：10.1073/pnas.0731830100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Proliferation of pluripotent, bone marrow stem cells, which develop to lymphoid and myeloid progenitors, is negatively regulated by estrogen. Although in estrogen deficiency and in estrogen receptor knockout mice there is significant alteration in bone marrow hematopoiesis, the effects of aging on estrogen receptor deficiencies in mice have not been investigated yet. In this study we show that by 1.5 years of age, estrogen receptor {beta} knockout (ER{beta}-/-) mice develop pronounced splenomegaly that is much more severe in females than in males. Further characterization of these mice revealed myelogenous hyperplasia in bone marrow, an increase in the number of granulocytes and B lymphocytes in blood, lymphadenopathy, and infiltration of leukocytes in the liver and lung. Analysis by flow cytometry of the bone marrow cells revealed that the percentage and total number of Gr-1hi/Mac-1hi-positive granulocytes were increased by 15-30% and 100%, respectively. The numbers of B cells in the bone marrow and spleen were significantly higher in ER{beta}-/- mice than in WT littermates. Some of the ER{beta}-/- mice also had a severe lymphoproliferative phenotype. Thus the absence of ER{beta} results in a myeloproliferative disease resembling human chronic myeloid leukemia with lymphoid blast crisis. Our results indicate a previously unknown role for ER{beta} in regulating the differentiation of pluripotent hematopoietic progenitor cells and suggest that the ER{beta}-/- mouse is a potential model for myeloid and lymphoid leukemia. Furthermore, we suggest that ER{beta} agonists might have clinical value in the treatment of leukemia.
