급성 골수성백혈병에서 Stem Cell Factor가 CD34+세포의 증식 및 IL-1β, IL-4, TNF-α의 분비에 미치는 효과

Abstract

Background: Stem cell factor(SCF) has a preferential effect on the proliferation of several classes of immature hematopoietic progenitor cells in combination with granulocyte-macrophage colonystimulating factor(GM-CSF) and/or interleukin(IL)-3. Secretion of immunornodulatory cytokines, such as IL- lβ, IL-4 and tumor necrosis factor(TNH)-α, may be important for regulation of proliferative responses in acute myelogenous leukemia(AML) blasts. Material and Method: To analyze the costimulatory role of SCF in leukemic growth, we investigated the effect of SCF in the presence of GM-CSF and/or IL-3 on isolated CD34+ leukemic blasts from the bone marrows of 15 patients with AML and 10 normal persons by immunomagnetic bead method. Also we evaluated the correlation between the leukemic growth and the secretion of IL-lβ, IL-4 and TNF-α from CD34+ blasts in the presence of SCF. Results: 1) In six cases(40%), CD34+ AML blasts responded with a significant increase in DNA synthesis and/or colony formation when SCF was used with GM-CSF and/or IL-3 relative to the growth with SCF alone; This result was compatible with those CD34+ normal bone marrow cells. 2) Spontaneous in vitro secretion of IL-lβ, IL-4 and TNF-α from CD34+ AML blasts showed a wide variation. SCF increased concentrations of IL- lβ, IL-4 and TNF-α in a minority of AML patients. 3) CD34+ AML blasts were cultured with SCF+GM-CSF, SCF +1L-3, and SCF+GM-CSF+IL-3, but a clear synergistic or additive effect of SCF on GM-CSF and/or IL-3 stimulated IL- lβ, IL-4 and TNF-α secretion could not be detected. Conclusion: Our results could support that the costimulating effect of SCF in the presence of GM-CSF and/or IL-3 was not related to the secretion of IL- lβ, IL-4 and TNF-α from CD34+ AML blasts.