Monoclonal antibody to the interferon-inducible protein Leu-13 triggers aggregation and inhibits proliferation of leukemic B cells.
Monoclonal antibody to the interferon-inducible protein Leu-13 triggers aggregation and inhibits proliferation of leukemic B cells.
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DOI：
10.1182/blood.v76.12.2583.2583
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发表时间：
1990-12
期刊：
影响因子：
20.3
通讯作者：
Sharon S. Evans;Deborah B. Lee;Tin Han;Thomas B Tomasi;Robert L. Evans
中科院分区：
文献类型：
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作者：
Sharon S. Evans;Deborah B. Lee;Tin Han;Thomas B Tomasi;Robert L. Evans
干扰素（IFN）-α抑制体外毛细胞中低分子量B细胞生长因子（BCGF）刺激的DNA合成，表明IFN-α在毛细胞白血病（HCL）中的治疗功效涉及恶性B细胞的生长抑制。16-Kd细胞表面蛋白Leu-13在T淋巴细胞中介导抗增殖信号，并且在内皮细胞中是IFN诱导的，这一证据促使我们研究该分子在白血病B细胞中的表达和功能作用。通过流式细胞术测定的Leu-13密度在体外和体内被来自HCL、慢性淋巴细胞白血病和幼淋巴细胞白血病患者的恶性B细胞上的IFN-α上调。单克隆抗Leu-13通过粘附途径触发白血病B细胞的同型聚集，该粘附途径不受白细胞功能相关抗原-1（LFA-1）或细胞间粘附分子-1（ICAM-1）抗体的抑制。此外，抗Leu-13增强IFN-α对BCG刺激的DNA合成的抑制作用，通过[3 H]-胸苷和[3 H]-脱氧腺苷掺入DNA进行评估。这些结果表明，Leu-13是一种新的IFN-诱导的信号通路的一部分，它可能会改变白血病B细胞在生理或治疗条件下的生长和粘附特性。
Interferon (IFN)-alpha inhibits DNA synthesis stimulated by low molecular weight B-cell growth factor (BCGF) in hairy cells in vitro, suggesting that the therapeutic efficacy of IFN-alpha in hairy cell leukemia (HCL) involves growth inhibition of malignant B cells. Evidence that the 16-Kd cell surface protein Leu-13 mediates an antiproliferative signal in T lymphocytes and is IFN-inducible in endothelial cells prompted us to examine the expression and functional role of this molecule in leukemic B cells. Leu-13 density, determined by flow cytometry, was upregulated in vitro and in vivo by IFN-alpha on malignant B cells from patients with HCL, chronic lymphocytic leukemia, and prolymphocytic leukemia. Monoclonal anti-Leu-13 triggered homotypic aggregation of leukemic B cells via an adhesion pathway that was not inhibited by antibodies to leukocyte function associated antigen-1 (LFA-1) or intercellular adhesion molecule-1 (ICAM-1). Moreover, anti-Leu-13 potentiated the inhibitory effects of IFN-alpha on BCGF-stimulated DNA synthesis, assessed by [3H]-thymidine and [3H]-deoxyadenosine incorporation into DNA. These results indicate that Leu-13 is part of a novel IFN-inducible signaling pathway which may modify the growth and adhesive properties of leukemic B cells under physiologic or therapeutic conditions.