Korean J Hematol 2001; 36(4):

Published online December 31, 2001

© The Korean Society of Hematology

장기간 골수배양법을 이용한 재생불량성빈혈의 병태생리학적 연구

홍대식, 이남수, 이규택, 박성규, 백승호, 원종호, 박희숙

순천향대학교 의과대학 내과학교실, 임상분자생물학연구소

Pathophysiologic Study of Anemia by Long-term Bone Marrow Cultures

Dae Sik Hong, Nam Su Lee, Kyu Tack Lee, Sung Kyu Park, Seung Ho Baick, Jong Ho Won, Hee Sook Park

Department of Internal Medicine and Institute of Clinical Molecular Biologic Research, College of Medicine, Soon Chun Hyang University, Seoul, Korea

Abstract

Background:
Several mechanisms have been proposed to account for bone marrow failure in aplastic anemia (AA), including deficiency in hematopoietic stem cells, a secondary stem cell defect involving immune regulation and defective marrow
stroma, or microenvironment. We investigated the pathophysiology of AA through long-term bone marrow cultures (LTBMCs) using bone marrow of AA patients before treatment and of patients responded to immunosuppressive therapy with anti-thymocyte globulin (ATG) and/or cyclosporine.
Methods:
We investigated the hematopoietic defect in severe aplastic anemia (SAA) patients by using long-term bone marrow cultures (LTBMCs). Twenty patients with SAA have been studied. In these patients, 10 had been treated with ATG plus cyclosporine and the remainders were studied before therapy was begun. Subsequent assays of the production of negative-acting hematopoietic cytokines (TNF-α, IFN-γ, MIP-1α and TGF-β) by AA stroma in LTBMCs were peformed.
Results:Initial assessment of CD34+ cells, CFU-GM and CFU-MK from LTBMCs in AA demonstrated severely reduced or absent in patients with SAA, even following hematologic recovery with immunosuppressive therapy, when compared with normal
controls. Significant difference in concentrations of TNF-α,IFN-γ, and MIP-1α between the AA and control groups were apparent. Interestingly, the levels of those negative-acting hematopoietic cytokines were decreased in SAA patients receiving immunosuppressive therapy, but not the levels of controls. However, the mean TGF-β concentrations in the AA patients and normal controls were not signficantly different. The percent of CD34+ cells and CFU-MK in bone marrow was lower in SAA patients before
immunosuppressive therapy was begun than that in SAA patients receiving immunosuppressive therapy and that in normal controls (mean 0.54±0.32% vs 0.96±0.32% vs 1.94±0.61%).
Conclusions:
These results indicate the presence of a in vitro
functional deficiency in the hematopoietic system of patients with AA, including those that achieved partial or complete remission after immunosuppressive treatment, and add to the available evidence for defect of microenvironment with hematopoeitic stem cell in some cases of AA.

Keywords Aplastic anemia, Long-term bone marrow cultures, Pathophysiology

Article

Korean J Hematol 2001; 36(4): 335-341

Published online December 31, 2001

Copyright © The Korean Society of Hematology.

장기간 골수배양법을 이용한 재생불량성빈혈의 병태생리학적 연구

홍대식, 이남수, 이규택, 박성규, 백승호, 원종호, 박희숙

순천향대학교 의과대학 내과학교실, 임상분자생물학연구소

Pathophysiologic Study of Anemia by Long-term Bone Marrow Cultures

Dae Sik Hong, Nam Su Lee, Kyu Tack Lee, Sung Kyu Park, Seung Ho Baick, Jong Ho Won, Hee Sook Park

Department of Internal Medicine and Institute of Clinical Molecular Biologic Research, College of Medicine, Soon Chun Hyang University, Seoul, Korea

Abstract

Background:
Several mechanisms have been proposed to account for bone marrow failure in aplastic anemia (AA), including deficiency in hematopoietic stem cells, a secondary stem cell defect involving immune regulation and defective marrow
stroma, or microenvironment. We investigated the pathophysiology of AA through long-term bone marrow cultures (LTBMCs) using bone marrow of AA patients before treatment and of patients responded to immunosuppressive therapy with anti-thymocyte globulin (ATG) and/or cyclosporine.
Methods:
We investigated the hematopoietic defect in severe aplastic anemia (SAA) patients by using long-term bone marrow cultures (LTBMCs). Twenty patients with SAA have been studied. In these patients, 10 had been treated with ATG plus cyclosporine and the remainders were studied before therapy was begun. Subsequent assays of the production of negative-acting hematopoietic cytokines (TNF-α, IFN-γ, MIP-1α and TGF-β) by AA stroma in LTBMCs were peformed.
Results:Initial assessment of CD34+ cells, CFU-GM and CFU-MK from LTBMCs in AA demonstrated severely reduced or absent in patients with SAA, even following hematologic recovery with immunosuppressive therapy, when compared with normal
controls. Significant difference in concentrations of TNF-α,IFN-γ, and MIP-1α between the AA and control groups were apparent. Interestingly, the levels of those negative-acting hematopoietic cytokines were decreased in SAA patients receiving immunosuppressive therapy, but not the levels of controls. However, the mean TGF-β concentrations in the AA patients and normal controls were not signficantly different. The percent of CD34+ cells and CFU-MK in bone marrow was lower in SAA patients before
immunosuppressive therapy was begun than that in SAA patients receiving immunosuppressive therapy and that in normal controls (mean 0.54±0.32% vs 0.96±0.32% vs 1.94±0.61%).
Conclusions:
These results indicate the presence of a in vitro
functional deficiency in the hematopoietic system of patients with AA, including those that achieved partial or complete remission after immunosuppressive treatment, and add to the available evidence for defect of microenvironment with hematopoeitic stem cell in some cases of AA.

Keywords: Aplastic anemia, Long-term bone marrow cultures, Pathophysiology

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