Selective hypersensitivity to granulocyte-macrophage colony-stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors.
Selective hypersensitivity to granulocyte-macrophage colony-stimulating factor by juvenile chronic myeloid leukemia hematopoietic progenitors.
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DOI：
10.1182/blood.v77.5.925.925
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发表时间：
1991-03
期刊：
影响因子：
20.3
通讯作者：
P. Emanuel;Lana J. Bates;R. Castleberry;R. Gualtieri;K. Zuckerman
中科院分区：
文献类型：
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作者：
P. Emanuel;Lana J. Bates;R. Castleberry;R. Gualtieri;K. Zuckerman
幼年型慢性粒细胞白血病（JCML）是研究骨髓增殖的良好模型，因为 JCML 造血祖细胞在体外以非常低的细胞密度生长，无需添加外源刺激。先前的研究表明，这种增殖依赖于粒细胞巨噬细胞集落刺激因子（GM-CSF），并且在培养前从细胞群中去除单核细胞可以消除这种“自发”骨髓增殖，这表明单核细胞刺激具有旁分泌作用。然而，随后的研究表明，JCML 单核细胞产生的 GM-CSF 增加并不是一个一致的发现，因此不是一个合理的唯一机制。在检查造血生长因子剂量反应曲线时，JCML GM 和红系非贴壁祖细胞群均表现出对 GM-CSF 的显着选择性超敏反应。对 IL-3 和 G-CSF 的反应与对照剂量反应曲线相同。这是骨髓性白血病的首次证明，其中对特定生长因子的超敏反应似乎与该疾病的发病机制有关。
Juvenile chronic myelogenous leukemia (JCML) is a good model for the study of myeloproliferation because JCML hematopoietic progenitor cells grow in vitro at very low cell densities without the addition of exogenous stimulus. Previous studies have demonstrated that this proliferation is dependent on granulocyte-macrophage colony-stimulating factor (GM-CSF), and that removal of monocytes from the cell population before culture eliminates this "spontaneous" myeloproliferation, suggesting a paracrine role of monocyte stimulation. However, subsequent studies have shown that increased GM-CSF production from the JCML monocytes is not a consistent finding and therefore not a plausible sole mechanism. In examining hematopoietic growth factor dose-response curves, both JCML GM and erythroid nonadherent progenitor cell populations displayed a marked and selective hypersensitivity to GM-CSF. Responses to interleukin-3 and G-CSF were identical to control dose-response curves. This is the first demonstration of a myeloid leukemia in which hypersensitivity to a specific growth factor appears to be involved in the pathogenesis of the disease.