Basic fibroblast growth factor is expressed by CD19/CD11c-positive cells in hairy cell leukemia
Basic fibroblast growth factor is expressed by CD19/CD11c-positive cells in hairy cell leukemia
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DOI：
10.1182/blood.v94.3.1077.415k06_1077_1085
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发表时间：
1999-08-01
期刊：
影响因子：
20.3
通讯作者：
Berger, R
中科院分区：
文献类型：
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作者：
Gruber, G;Schwarzmeier, JD;Berger, R
毛细胞白血病 (HCL) 有几个特征。其中包括全血细胞减少症、骨髓纤维化以及外周血（PB）、骨髓（BM）和脾脏中出现明确的肿瘤细胞表型。毛细胞 (HC) 共表达 B 淋巴细胞和单核细胞/巨噬细胞特异性抗原，因此恶性细胞似乎并不局限于特定的谱系。当通过酶联免疫吸附测定 (ELISA) 筛选血清或骨髓抽吸物中的碱性成纤维细胞生长因子 (bFGF) 时，来自 HCL 的样本（血清：平均值，29 pg/mL；骨髓抽吸物：平均值，641 pg/mL）的含量显着高于健康受试者的水平。为了研究来自 HCL 患者和健康供体 (HD) 的外周血单核细胞 (PBMC) 是否能够产生 bFGF，测试了培养上清液（条件培养基，[CMI）中是否存在这种细胞因子。虽然在 HD 细胞培养物中检测不到 bFGF，但 HCL 衍生的 CM 含有相对较高水平的 bFGF。 CM 成功地用于刺激间充质细胞增殖，这种增殖可以被中和性抗 bFGF 抗体抑制。美洲商陆有丝分裂原 (PWM) 或 12-o-十四烷酰基佛波醇-13-乙酸酯 (TPA) 加钙离子载体 (Ca-lp) 组合的细胞激活导致 mRNA 表达增强。 Western blot实验结果表明，HC至少合成三种亚型（大约18、23和25 kD），但仅输出23 kD亚型。为了评估生产细胞的性质，使用 bFGF 特异性和抗 CD11c 单克隆抗体 (MoAb) 进行双重免疫荧光分析。大多数 CD11c 评分呈阳性的细胞也与抗 bFGF MoAb 发生反应。此外，CD19/CD11c 阳性细胞的富集与 bFGF 水平的增强相关，从而支持 HC 是 bFGF 产生细胞的论点。HCL 中 bFGF 的生物学功能可能是介导化疗耐药性，因为 2-氯脱氧腺苷 (5-CdA) 诱导的细胞增殖抑制可以被 bFGF 逆转。 HC 产生的内源性 bFGF 不受这种嘌呤类似物的影响，并且与正常 PBMC 相比，产生 bFGF 的 HC 中 2-CdA 诱导的细胞凋亡减少。因此，HC 的 bFGF 表达可能对于恶性细胞的化疗耐药性和存活很重要。 (C) 1999 年，美国血液学会。
Several features are characteristic for hairy cell leukemia (HCL). Among those are pancytopenia, bone marrow fibrosis, and the appearance of a defined tumor cell phenotype in peripheral blood (PB), bone marrow (BM), and spleen. Hairy cells (HC) coexpress antigens specific for B lymphocytes and monocytes/macrophages and thus the malignant cell does not seem to be restricted to a defined lineage. When serum or bone marrow aspirate was screened by enzyme-linked immunosorbent assay (ELISA) for basic fibroblast growth factor (bFGF), specimen derived from HCL (serum: mean value, 29 pg/mL; BM aspirate: mean value, 641 pg/mL) contained significantly higher levels than those from healthy subjects. To study whether peripheral blood mononuclear cells (PBMC) derived from patients suffering from HCL and healthy donors (HD) were capable of producing bFGF, culture supernatant (conditioned medium, [CMI) was tested for the presence of this cytokine. While bFGF was not detectable in cell cultures from HD, HCL-derived CM contained relatively high levels of bFGF. CM was successfully used for stimulation of mesenchymal cell proliferation, which could be inhibited by a neutralizing anti-bFGF antibody. Cellular activation by pokeweed mitogen (PWM) or the combination of 12-o-tetradecanoyl-phorbol-13-acetate (TPA) plus calcium ionophore (Ca-lp) led to an enhanced mRNA expression. Results of Western blot experiments showed that HC synthesize at least three isoforms (approximately 18, 23, and 25 kD), but only the 23-kD isoform is exported. To assess the nature of the producer cell, double immunofluorescence analysis using a bFGF-specific and an anti-CD11c monoclonal antibody (MoAb) was undertaken. The majority of cells scoring positive for CD11c were also reactive with the anti-bFGF MoAb. Furthermore, enrichment of CD19/CD11c-positive cells correlated with enhanced bFGF levels, thereby supporting the argument for HC being the producer cells of bFGF A biological function of bFGF in HCL might be mediation of chemoresistance, as 2-chlorodeoxyadenosine (5-CdA)-induced inhibition of cell proliferation can be reversed by bFGF. Endogenous bFGF production by HC is not affected by this purine analogue and 2-CdA-induced apoptosis is diminished in bFGF-producing HC as compared with normal PBMC. Therefore, bFGF expression by HC might be important for resistance to chemotherapy and survival of the malignant cells. (C) 1999 by The American Society of Hematology.