Disruption of the Estrogen Receptor β Gene in Mice Causes Myeloproliferative Disease Resembling Chronic Myeloid Leukemia with Lymphoid Blast Crisis
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 β knockout (ERβ-/-) 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 ERβ-/-mice than in WT littermates. Some of the ERβ-/-mice also had a severe lymphoproliferative phenotype. Thus the absence of ERβ results in a myeloproliferative disease resembling human chronic myeloid leukemia with lymphoid blast crisis. Our results indicate a previously unknown role for ERβ in regulating the differentiation of pluripotent hematopoietic progenitor cells and suggest that the ERβ-/-mouse is a potential model for myeloid and lymphoid leukemia. Furthermore, we suggest that ERβ agonists might have clinical value in the treatment of leukemia..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2003 |
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| Erschienen: |
2003 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:100 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shim, Gil-Jin [VerfasserIn] |
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| Links: |
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| Themen: |
Biological sciences |
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| 245 | 1 | 0 | |a Disruption of the Estrogen Receptor β Gene in Mice Causes Myeloproliferative Disease Resembling Chronic Myeloid Leukemia with Lymphoid Blast Crisis |
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| 520 | |a 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 β knockout (ERβ-/-) 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 ERβ-/-mice than in WT littermates. Some of the ERβ-/-mice also had a severe lymphoproliferative phenotype. Thus the absence of ERβ results in a myeloproliferative disease resembling human chronic myeloid leukemia with lymphoid blast crisis. Our results indicate a previously unknown role for ERβ in regulating the differentiation of pluripotent hematopoietic progenitor cells and suggest that the ERβ-/-mouse is a potential model for myeloid and lymphoid leukemia. Furthermore, we suggest that ERβ agonists might have clinical value in the treatment of leukemia. | ||
| 540 | |a Copyright 1993-2003 National Academy of Sciences of the United States of America | ||
| 650 | 4 | |a Medical Sciences | |
| 650 | 4 | |a Biological sciences |x Biology |x Anatomy |x Body tissues |x Connective tissues |x Bones |x Bone marrow | |
| 650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Hematologic diseases |x Bone marrow diseases |x Myeloproliferative disorders | |
| 650 | 4 | |a Biological sciences |x Biochemistry |x Biomolecules |x Hormones |x Steroid hormones |x Sex hormones |x Gonadal steroid hormones |x Estrogens | |
| 650 | 4 | |a Biological sciences |x Biology |x Physiology |x Body composition |x Body fluids |x Blood | |
| 650 | 4 | |a Health sciences |x Medical conditions |x Diseases |x Neoplasia |x Cancer |x Leukemia |x Myeloid leukemia |x Chronic myeloid leukemia | |
| 650 | 4 | |a Biological sciences |x Biology |x Cytology |x Cell biology |x Cells |x Stem cells |x Multipotent stem cells |x Myeloid cells | |
| 650 | 4 | |a Biological sciences |x Biology |x Physiology |x Body composition |x Body fluids |x Blood |x Blood cells |x Leukocytes |x Mononuclear leukocytes |x Lymphocytes |x B lymphocytes | |
| 650 | 4 | |a Biological sciences |x Biology |x Physiology |x System physiology |x Cardiovascular physiology |x Circulatory system |x Lymphatic system |x Spleen | |
| 650 | 4 | |a Biological sciences |x Biology |x Zoology |x Animals |x Mammals |x Rodents |x Mice | |
| 650 | 4 | |a Biological sciences |x Biology |x Physiology |x Body composition |x Body fluids |x Blood |x Blood cells |x Leukocytes |x Mononuclear leukocytes |x Lymphocytes |x Biological Sciences | |
| 655 | 4 | |a research-article | |
| 700 | 1 | |a Wang, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Andersson, Sandra |e verfasserin |4 aut | |
| 700 | 1 | |a Nagy, Noémi |e verfasserin |4 aut | |
| 700 | 1 | |a Kis, Loránd Levente |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qinghong |e verfasserin |4 aut | |
| 700 | 1 | |a Mäkelä, Sari |e verfasserin |4 aut | |
| 700 | 1 | |a Warner, Margaret |e verfasserin |4 aut | |
| 700 | 1 | |a Gustafsson, Jan-Åke |e verfasserin |4 aut | |
| 773 | 1 | 8 | |g volume:100 |g year:2003 |g number:11 |g pages:6694-6699 |
| 856 | 4 | 0 | |u https://www.jstor.org/stable/3144127 |3 Volltext |
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