Min Y H, Lee S T, Lee B K, Chong S Y, Lee S, Hahn J S, Ko Y W
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Yonsei Med J. 1995 Mar;36(1):26-36. doi: 10.3349/ymj.1995.36.1.26.
Stem cell factor (SCF), a c-kit ligand, has a preferential effect on the proliferation of several classes of immature hematopoietic progenitor cells in combination with GM-CSF or IL-3. 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-positive (CD34+) leukemic blasts from 15 patients with acute myelogenous leukemia (AML). Cultures of CD34+ cells from normal bone marrow were used as controls. When the proliferation of CD34+ AML blasts in the presence of GM-CSF and/or IL-3 were evaluated in vitro for the effects of SCF, two patterns emerged. In one pattern, 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 is consistent with those CD34+ bone marrow cells from normal donors. Six patients (40%) were included in this category. The addition of SCF as a single factor resulted in colony formation in all six of these cases. In the other pattern, nine of the patients (60%) had CD34+ leukemic cells whose growth with SCF plus either GM-CSF, IL-3, or GM-CSF+IL-3, was not significantly different from the growth noted in the presence of SCF alone. Among them seven cases that did not form colonies in response to SCF alone, and one case showing autocrine, background growth were included. In the six cases in which the costimulating effects of SCF were documented, CD34+ c-kit+ blasts comprised 50.5 +/- 18.7% of the CD34+ leukemic blasts-higher than 21.8 +/- 19.4% of cases in which the costimulating effect of SCF was not documented. In the cases showing high c-kit antigen expression (> or = 40%), SCF had a costimulatory effect in 71% (5/7) of the patients. In conclusion, our data indicate that CD34+ leukemic blasts from a good proportion of patients with AML did not respond to the costimulating effects of SCF in the presence of GM-CSF adn/or IL-3, in contrast to those CD34+ bone marrow cells from normal donors. The possible use of SCF for acute leukemia must await further cytogenetic and molecular studies, which should clarify the preferential costimulating role of SCF in normal hematopoiesis.
干细胞因子（SCF）是一种c-kit配体，与粒细胞-巨噬细胞集落刺激因子（GM-CSF）或白细胞介素-3（IL-3）联合使用时，对几类未成熟造血祖细胞的增殖具有优先作用。为了分析SCF在白血病生长中的共刺激作用，我们研究了在GM-CSF和/或IL-3存在的情况下，SCF对15例急性髓性白血病（AML）患者分离出的CD34阳性（CD34+）白血病原始细胞的影响。来自正常骨髓的CD34+细胞培养物用作对照。当在体外评估GM-CSF和/或IL-3存在时SCF对CD34+ AML原始细胞增殖的影响时，出现了两种模式。在一种模式中，当SCF与GM-CSF和/或IL-3联合使用时，相对于单独使用SCF时的生长，CD34+ AML原始细胞的DNA合成和/或集落形成显著增加；这一结果与正常供体的CD34+骨髓细胞一致。六名患者（40%）属于这一类。在所有这六个病例中，单独添加SCF均导致集落形成。在另一种模式中，九名患者（60%）的CD34+白血病细胞在SCF加GM-CSF、IL-3或GM-CSF + IL-3存在下的生长与单独使用SCF时的生长无显著差异。其中包括七例单独使用SCF时未形成集落的病例，以及一例显示自分泌背景生长的病例。在记录到SCF共刺激作用的六个病例中，CD34+ c-kit+原始细胞占CD34+白血病原始细胞的50.5±18.7%，高于未记录到SCF共刺激作用病例的21.8±19.4%。在显示高c-kit抗原表达（≥40%）的病例中，71%（5/7）的患者SCF具有共刺激作用。总之，我们的数据表明，与正常供体的CD34+骨髓细胞不同，相当一部分AML患者的CD34+白血病原始细胞在GM-CSF和/或IL-3存在的情况下对SCF的共刺激作用无反应。SCF用于急性白血病的可能性必须等待进一步的细胞遗传学和分子研究，这些研究应阐明SCF在正常造血中的优先共刺激作用。
