Murohashi I, Endoh K, Feng M, Yoshida K, Hirota H, Yoshida S, Jinnai I, Bessho M, Hirashima K
First Department of Internal Medicine, Saitama Medical School, Japan.
J Interferon Cytokine Res. 1995 Oct;15(10):829-35. doi: 10.1089/jir.1995.15.829.
We investigated the effects of stem cell factor (SCF) on the growth of blast clonogenic cells from 27 patients with acute myeloblastic leukemia (AML) and 3 patients with chronic myelocytic leukemia in myeloid crisis. SCF alone showed a significant stimulatory activity in 15 of 30 patients (50%). A marked reduction in the number of blast cell colonies supported by SCF alone was noted by the addition of neutralizing antibody (Ab) against granulocyte-macrophage colony-stimulating factor (GM-CSF). Ab against interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) also moderately reduced the number of colonies, whereas Ab against granulocyte CSF (G-CSF) failed to do so. All four Ab together completely abolished the growth in 5 of 6 patients tested. c-kit antisense oligonucleotides reduced the colony formation supported by IL-3 or G-CSF or, in the absence of growth factor, in only 2 of 10 patients tested. SCF caused stimulation by acting synergistically with G-CSF, GM-CSF, IL-3, IL-6, IL-9, IL-11, and IL-12 in 20 of 27 (74%), 17 of 27 (63%), 14 of 28 (50%), 9 of 28 (32%), 1 of 15 (7%), 3 of 28 (11%), and 2 of 15 (13%) patients, respectively. Thus, SCF alone or in combination with some other factor stimulated the growth in 27 of 30 (90%) patients. Of 3 nonresponders, 2 were AML, M3 at presentation. G-CSF at the optimal concentration increased the sensitivity of blasts to SCF. Taken together, SCF acting in combination with other factors, but not alone, stimulates the growth of blast clonogenic cells. GM-CSF, IL-6, and TNF-alpha may be produced endogenously, whereas G-CSF and SCF may be supplied exogenously. Autocrine regulation of the growth of blasts seems to increase the responsiveness of the cells to any of these factors, allowing them to achieve a highly active growth state.
我们研究了干细胞因子（SCF）对27例急性髓细胞白血病（AML）患者和3例处于髓系危象的慢性粒细胞白血病患者的原始克隆形成细胞生长的影响。单独使用SCF时，30例患者中有15例（50%）显示出显著的刺激活性。加入抗粒细胞-巨噬细胞集落刺激因子（GM-CSF）的中和抗体（Ab）后，单独由SCF支持的原始细胞集落数量显著减少。抗白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的抗体也适度减少了集落数量，而抗粒细胞集落刺激因子（G-CSF）的抗体则没有。在6例测试患者中，所有四种抗体共同作用完全消除了其中5例的生长。c-kit反义寡核苷酸仅在10例测试患者中的2例中减少了由IL-3或G-CSF支持的集落形成，或在无生长因子的情况下减少了集落形成。SCF分别与G-CSF、GM-CSF、IL-3、IL-6、IL-9、IL-11和IL-12协同作用，在27例患者中的20例（74%）、27例患者中的17例（63%）、28例患者中的14例（50%）、28例患者中的9例（32%）、15例患者中的1例（7%）、28例患者中的3例（11%）和15例患者中的2例（13%）中引起刺激。因此，单独使用SCF或与其他一些因子联合使用可刺激30例患者中的27例（90%）生长。在3例无反应者中，2例初诊时为AML，M3型。最佳浓度的G-CSF增加了原始细胞对SCF的敏感性。综上所述，SCF与其他因子联合作用而非单独作用可刺激原始克隆形成细胞的生长。GM-CSF、IL-6和TNF-α可能内源性产生，而G-CSF和SCF可能外源性提供。原始细胞生长的自分泌调节似乎增加了细胞对这些因子中任何一种的反应性，使其达到高度活跃的生长状态。
