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KMID : 0882419930440030327
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Korean Journal of Medicine
1993 Volume.44 No. 3 p.327 ~ p.346
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The Effects of GM-CSF on the Long-Term Bone Marrow Cultures in Acute Leukemia
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Ko Yun-Woong
Lee Sun-Ju
Hahn Jee-Sook
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Abstract
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Background : Significant chagnes in leukemic cell behaviour have been reported to occur during long-term cultures of bone marrow from patients with AML. Recent reports of intensive therapy and hematopoietc rescue with autologous marrow cells grown in the longterm bone marrow culture (LTBMC) system have aroused much attention. But its
effectiveness as a means to purging leukemic cells and expanmsion of regenerating normal hemopoietic series should be increased for better autotransplant outcomes. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is crucial in the regulation of proliferation and maturation of normal hematopoietic progenitor cells. It also exerts profound stimulative effects on leukemic cells, and renders them more susceptible to purging agents. To evaluate the effects of GM-CSF on the LTBMC-mediated myelopoietc recoveries and purging of leukemic cells, we studied the effects of GM-CSF priming on long-term cultures of acute leukemic bone marrow cells.
Methods : The mononuclear bone marrow cells of 22 patients with acute leukemia were incubated with 100 ng/ml GM-CSF for 24 hours. After preincubation, the LTBMCs were started in 25 cm^2-culture flask in 10 ml culture medium supplemented with 12.5% horse serum at 37C. Over a period of 4 weeks, the LTBMCs were demipopulated and replaced by fresh medium weekly. Adherent layers were examined in situ by inverted microscopy of flask bases during the course of the study. Nonadherent cells recovered after feeding were counted, and plated in clonogenic assays and differentail morphologic counts were performed on cytospin preparation. Adherent layer cells were obtained by detaching at the termination of cultures by incubation with collagenase.
Results : We found that GM-CSF predominantly influenced initial increase in (a) the number of nonadherent cells, (b) the number of terminally differentiated granulocytes (band and segmented neuttrophils), and (c) the number of nonadherent granulocyte-macrophage colony-forming units (CFU-GM) consisted of myeloid cells morphologically identical to normal control cultrues consisderably (p<0.05) in LTBMC before the establishment of a confluent adherent layer. And GM-CSF priming tended to decrease the number of nonadherent leukemic colony-forming units in 1-week-old LTBMC, which is not statistically significant. These effects were lost after 2 weeks of LTBMC.
Conclusion : GM-CSF priming of leukemic cells prior to LTBMC may be more effective for purging leukemic cells and expanding myeloid recoveries than without GM-CNF, but its effects were restricted before the establishment of confulent adherent layers. Its transient effects sugtgest that GM-CNF may not be active on primitive hemopoietic stem cells
responsible for LTBMC propagation. Alternatively, stromal cells may exert tight regulatory control over progenitor cells. Further analysis will be required to enhance recovery of normal myelopoiesis and to decrease survival of leukemic progenitor cells more effectively on the basis of combined use with different hemopoietic grouth factors or with other various cytokines.
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KEYWORD
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GM-CSF, Long-term bone marrove culture, Acute leukemia, Purging
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