ALTERATIONS IN THE BONE MARROW MICROENVIRONMENT CAN ELICIT DEFECTIVE HEMATOPOIESIS: COMPARISON OF APLASTIC ANEMIA, CHRONIC MYELOID LEUKEMIA AND NORMAL BONE MARROW.
(Abstract release date: 05/21/15)
EHA Library. Park M. 06/12/15; 102709; PB1771
Disclosure(s): Chungbuk National Univ.
Meerim Park
Contributions
Contributions
Abstract
Abstract: PB1771
Type: Publication Only
Background
Normal hematopoiesis involves complex interactions between hematopoietic cells and the bone marrow (BM) microenvironment. Examples of extremes at both ends of dysregulated hematopoiesis are BM failure in aplastic anemia (AA) and myeloproliferative disease such as chronic myeloid leukemia (CML). The specific causes of and mechanisms involved in dysregulated hematopoiesis are unknown.
Aims
To better understand the interactions between hematopoiesis and the BM microenvironment, we investigated changes in the hematopoietic stem cell (HSC) compartment and the BM microenvironment of patients with AA (n=10), CML in chronic phase (n=10) and normal marrow (n=10).
Methods
BM biopsy specimens were analyzed by semiquantitative immunohistochemistry (mean positive cell number/high power field) for osteopontin, osteonectin, osteocalcin, nestin, stromal-derived factor-1 (SDF-1) expression, and to identify endothelial cells, lymphocytes (CD3, CD4, CD8, CD20, CD56), macrophage (CD169), and HSCs (CD34, CD117).
Results
The lowest numbers of HSCs were in AA specimens, and the highest numbers were in CML specimens. The highest numbers of T and B lymphocytes were found in normal control specimens (p<0.01). Natural killer (NK) cells were occasionally observed in the AA specimens, but were absent from the CML and control specimens (p<0.01). Macrophages were absent from the CML specimens, whereas the number of macrophages (p<0.01) was highest in the AA specimens. There were significant differences between the stromal cell components of AA specimens and CML specimens. Numbers of cells positive for osteopontin (p<0.01), SDF-1 (p<0.01) and nestin (p<0.01) expression were higher in the AA than in the CML specimens. No nestin+ cells were observed in CML specimens. Numbers of cells positive for osteocalcin (p<0.01) and osteonectin (p=0.015) expression were higher in CML than in AA specimens. The highest numbers of endothelial cells were in CML specimens (p<0.01).
Summary
The BM of AA patients demonstrated increased numbers of macrophages and NK cells, which could result in cytotoxic and/or immune-mediated marrow damage; or, alternatively, be a consequence of HSC injury. The BM of CML patients demonstrated decreased numbers of SDF-1-expressing and absence of nestin-expressing cells, which may result in reduced homing of HSCs and proliferation of malignant hematopoietic cells. There were significant differences between AA and CML specimens in the numbers of cells expressing osteoblast-derived extracellular proteins such as osteopontin, osteocalcin and osteonectin. Our findings suggest that changes in the components of the BM microenvironment might be related to defective hematopoiesis that may lead to BM failure and/or myeloproliferative disease.
Keyword(s): Aplastic anemia, Chronic myeloid leukemia, Hematopoiesis, Microenvironment
Type: Publication Only
Background
Normal hematopoiesis involves complex interactions between hematopoietic cells and the bone marrow (BM) microenvironment. Examples of extremes at both ends of dysregulated hematopoiesis are BM failure in aplastic anemia (AA) and myeloproliferative disease such as chronic myeloid leukemia (CML). The specific causes of and mechanisms involved in dysregulated hematopoiesis are unknown.
Aims
To better understand the interactions between hematopoiesis and the BM microenvironment, we investigated changes in the hematopoietic stem cell (HSC) compartment and the BM microenvironment of patients with AA (n=10), CML in chronic phase (n=10) and normal marrow (n=10).
Methods
BM biopsy specimens were analyzed by semiquantitative immunohistochemistry (mean positive cell number/high power field) for osteopontin, osteonectin, osteocalcin, nestin, stromal-derived factor-1 (SDF-1) expression, and to identify endothelial cells, lymphocytes (CD3, CD4, CD8, CD20, CD56), macrophage (CD169), and HSCs (CD34, CD117).
Results
The lowest numbers of HSCs were in AA specimens, and the highest numbers were in CML specimens. The highest numbers of T and B lymphocytes were found in normal control specimens (p<0.01). Natural killer (NK) cells were occasionally observed in the AA specimens, but were absent from the CML and control specimens (p<0.01). Macrophages were absent from the CML specimens, whereas the number of macrophages (p<0.01) was highest in the AA specimens. There were significant differences between the stromal cell components of AA specimens and CML specimens. Numbers of cells positive for osteopontin (p<0.01), SDF-1 (p<0.01) and nestin (p<0.01) expression were higher in the AA than in the CML specimens. No nestin+ cells were observed in CML specimens. Numbers of cells positive for osteocalcin (p<0.01) and osteonectin (p=0.015) expression were higher in CML than in AA specimens. The highest numbers of endothelial cells were in CML specimens (p<0.01).
Summary
The BM of AA patients demonstrated increased numbers of macrophages and NK cells, which could result in cytotoxic and/or immune-mediated marrow damage; or, alternatively, be a consequence of HSC injury. The BM of CML patients demonstrated decreased numbers of SDF-1-expressing and absence of nestin-expressing cells, which may result in reduced homing of HSCs and proliferation of malignant hematopoietic cells. There were significant differences between AA and CML specimens in the numbers of cells expressing osteoblast-derived extracellular proteins such as osteopontin, osteocalcin and osteonectin. Our findings suggest that changes in the components of the BM microenvironment might be related to defective hematopoiesis that may lead to BM failure and/or myeloproliferative disease.
Keyword(s): Aplastic anemia, Chronic myeloid leukemia, Hematopoiesis, Microenvironment
Abstract: PB1771
Type: Publication Only
Background
Normal hematopoiesis involves complex interactions between hematopoietic cells and the bone marrow (BM) microenvironment. Examples of extremes at both ends of dysregulated hematopoiesis are BM failure in aplastic anemia (AA) and myeloproliferative disease such as chronic myeloid leukemia (CML). The specific causes of and mechanisms involved in dysregulated hematopoiesis are unknown.
Aims
To better understand the interactions between hematopoiesis and the BM microenvironment, we investigated changes in the hematopoietic stem cell (HSC) compartment and the BM microenvironment of patients with AA (n=10), CML in chronic phase (n=10) and normal marrow (n=10).
Methods
BM biopsy specimens were analyzed by semiquantitative immunohistochemistry (mean positive cell number/high power field) for osteopontin, osteonectin, osteocalcin, nestin, stromal-derived factor-1 (SDF-1) expression, and to identify endothelial cells, lymphocytes (CD3, CD4, CD8, CD20, CD56), macrophage (CD169), and HSCs (CD34, CD117).
Results
The lowest numbers of HSCs were in AA specimens, and the highest numbers were in CML specimens. The highest numbers of T and B lymphocytes were found in normal control specimens (p<0.01). Natural killer (NK) cells were occasionally observed in the AA specimens, but were absent from the CML and control specimens (p<0.01). Macrophages were absent from the CML specimens, whereas the number of macrophages (p<0.01) was highest in the AA specimens. There were significant differences between the stromal cell components of AA specimens and CML specimens. Numbers of cells positive for osteopontin (p<0.01), SDF-1 (p<0.01) and nestin (p<0.01) expression were higher in the AA than in the CML specimens. No nestin+ cells were observed in CML specimens. Numbers of cells positive for osteocalcin (p<0.01) and osteonectin (p=0.015) expression were higher in CML than in AA specimens. The highest numbers of endothelial cells were in CML specimens (p<0.01).
Summary
The BM of AA patients demonstrated increased numbers of macrophages and NK cells, which could result in cytotoxic and/or immune-mediated marrow damage; or, alternatively, be a consequence of HSC injury. The BM of CML patients demonstrated decreased numbers of SDF-1-expressing and absence of nestin-expressing cells, which may result in reduced homing of HSCs and proliferation of malignant hematopoietic cells. There were significant differences between AA and CML specimens in the numbers of cells expressing osteoblast-derived extracellular proteins such as osteopontin, osteocalcin and osteonectin. Our findings suggest that changes in the components of the BM microenvironment might be related to defective hematopoiesis that may lead to BM failure and/or myeloproliferative disease.
Keyword(s): Aplastic anemia, Chronic myeloid leukemia, Hematopoiesis, Microenvironment
Type: Publication Only
Background
Normal hematopoiesis involves complex interactions between hematopoietic cells and the bone marrow (BM) microenvironment. Examples of extremes at both ends of dysregulated hematopoiesis are BM failure in aplastic anemia (AA) and myeloproliferative disease such as chronic myeloid leukemia (CML). The specific causes of and mechanisms involved in dysregulated hematopoiesis are unknown.
Aims
To better understand the interactions between hematopoiesis and the BM microenvironment, we investigated changes in the hematopoietic stem cell (HSC) compartment and the BM microenvironment of patients with AA (n=10), CML in chronic phase (n=10) and normal marrow (n=10).
Methods
BM biopsy specimens were analyzed by semiquantitative immunohistochemistry (mean positive cell number/high power field) for osteopontin, osteonectin, osteocalcin, nestin, stromal-derived factor-1 (SDF-1) expression, and to identify endothelial cells, lymphocytes (CD3, CD4, CD8, CD20, CD56), macrophage (CD169), and HSCs (CD34, CD117).
Results
The lowest numbers of HSCs were in AA specimens, and the highest numbers were in CML specimens. The highest numbers of T and B lymphocytes were found in normal control specimens (p<0.01). Natural killer (NK) cells were occasionally observed in the AA specimens, but were absent from the CML and control specimens (p<0.01). Macrophages were absent from the CML specimens, whereas the number of macrophages (p<0.01) was highest in the AA specimens. There were significant differences between the stromal cell components of AA specimens and CML specimens. Numbers of cells positive for osteopontin (p<0.01), SDF-1 (p<0.01) and nestin (p<0.01) expression were higher in the AA than in the CML specimens. No nestin+ cells were observed in CML specimens. Numbers of cells positive for osteocalcin (p<0.01) and osteonectin (p=0.015) expression were higher in CML than in AA specimens. The highest numbers of endothelial cells were in CML specimens (p<0.01).
Summary
The BM of AA patients demonstrated increased numbers of macrophages and NK cells, which could result in cytotoxic and/or immune-mediated marrow damage; or, alternatively, be a consequence of HSC injury. The BM of CML patients demonstrated decreased numbers of SDF-1-expressing and absence of nestin-expressing cells, which may result in reduced homing of HSCs and proliferation of malignant hematopoietic cells. There were significant differences between AA and CML specimens in the numbers of cells expressing osteoblast-derived extracellular proteins such as osteopontin, osteocalcin and osteonectin. Our findings suggest that changes in the components of the BM microenvironment might be related to defective hematopoiesis that may lead to BM failure and/or myeloproliferative disease.
Keyword(s): Aplastic anemia, Chronic myeloid leukemia, Hematopoiesis, Microenvironment
{{ help_message }}
{{filter}}