Gualtieri R J, Castleberry R P, Gibbons J, Miller D M, Berkow R L, Parmley R T, Banks J
Department of Medicine, Children's Hospital of Alabama, University of Alabama, Birmingham 35294.
Exp Hematol. 1988 Aug;16(7):613-9.
Juvenile chronic myelogenous leukemia (JCML) may be distinguished from adult CML based upon in vitro cell growth characteristics. We studied four untreated children with JCML and report additional unique findings. Peripheral blood (PB) and bone marrow (BM) cells were grown in soft agar. Without exogenous colony-stimulating activity (CSA) there was exuberant "spontaneous" colony formation in both PB and BM cultures. In the absence of exogenous stimulus, PB colony morphology was predominantly, but not exclusively, monocyte/macrophage. When PB was depleted of adherent cells, "spontaneous" colony formation was nearly completely abrogated. Cultures were also performed in the presence of various sources of CSA including giant cell tumor-conditioned medium (GCT-CM), a melanoma cell line-CM (LD1-CM), human placenta-CM (HPCM), and normal PB mononuclear cell (PBMC) feeder layers. Colony formation was typically increased with HPCM and PBMC, whereas in two patients GCT-CM and LD1-CM failed to stimulate additional colony growth when compared to cultures without exogenous CSA and, in fact, appeared to inhibit baseline "spontaneous" growth. The morphology of colonies in the presence of exogenous stimuli was highly variable. Because of the recent association between the c-fms protooncogene product and the receptor for the monocyte growth factor CSF-1, we analyzed the PB cells from two JCML patients for c-fms expression. Although expressed, c-fms levels were less than that in an adult with Ph1-positive CML in chronic phase. These studies indicate that in JCML, there are dramatic increases in both PB and BM colony-forming cells and that "spontaneous" growth is dependent on an accessory adherent cell fraction. Furthermore, patterns of responsiveness to various sources of CSA suggest that the colony-forming cells may not be a uniform population of malignant cells.
青少年慢性粒细胞白血病（JCML）可根据体外细胞生长特性与成人慢性粒细胞白血病（CML）相区分。我们研究了4例未经治疗的JCML患儿，并报告了其他独特发现。外周血（PB）和骨髓（BM）细胞在软琼脂中培养。在没有外源性集落刺激活性（CSA）的情况下，PB和BM培养物中均出现旺盛的“自发”集落形成。在没有外源性刺激的情况下，PB集落形态主要但并非完全是单核细胞/巨噬细胞。当PB去除贴壁细胞后，“自发”集落形成几乎完全被消除。还在各种CSA来源存在的情况下进行培养，包括巨细胞瘤条件培养基（GCT-CM）、黑色素瘤细胞系CM（LD1-CM）、人胎盘CM（HPCM）和正常PB单个核细胞（PBMC）饲养层。集落形成通常在HPCM和PBMC存在时增加，而在2例患者中，与没有外源性CSA的培养物相比，GCT-CM和LD1-CM未能刺激额外的集落生长，事实上，似乎抑制了基线“自发”生长。在外源性刺激存在的情况下，集落形态高度可变。由于最近c-fms原癌基因产物与单核细胞生长因子CSF-1受体之间的关联，我们分析了2例JCML患者的PB细胞中c-fms的表达。虽然有表达，但c-fms水平低于1例慢性期Ph1阳性CML成人患者。这些研究表明，在JCML中，PB和BM集落形成细胞均显著增加，且“自发”生长依赖于辅助贴壁细胞部分。此外，对各种CSA来源的反应模式表明，集落形成细胞可能不是均匀的恶性细胞群体。
