Fournier S, Jackson J, Kumar A, King T, Sharma S, Biron G, Rubio M, Delespesse G, Sarfati M
University of Montreal, Notre-Dame Hospital, Laboratory for Allergy Research, Quebec, Canada.
Eur J Immunol. 1992 Jul;22(7):1927-30. doi: 10.1002/eji.1830220737.
The role of cytokines in the growth and spreading of human hematologic malignancies has been underlined in recent years. Here we report evidence that a human 12-kDa B cell growth factor (BCGF-12KD) may function as a growth stimulatory factor in B cell chronic lymphocytic leukemia (B-CLL). First, recombinant BCGF-12KD induced dose-dependent DNA synthesis in neoplastic B cells of four B-CLL patients tested. Second, seven different B-CLL clones secreted a BCGF-12KD-like product that accounted for their proliferation. A neutralizing monoclonal antibody (mAb; Ac8) directed against a BCGF-12KD synthetic peptide inhibited the spontaneous growth of the leukemic B cells. The same mAb blocked DNA synthesis in normal tonsillar B lymphocytes induced by the culture supernatant of spontaneously proliferating B-CLL cells. Finally, BCGF-12KD mRNA was expressed in freshly isolated (two of three patients) as well as in vitro proliferating B-CLL cells (three of three patients). These findings strongly suggest that BCGF-12KD can modulate the growth of B-CLL cells in vivo as well as in vitro. They may offer significant insights into the biology of this frequent B lymphoproliferative disorder.
近年来，细胞因子在人类血液系统恶性肿瘤生长和扩散中的作用已得到强调。在此，我们报告证据表明，一种人类12 kDa B细胞生长因子（BCGF - 12KD）可能在B细胞慢性淋巴细胞白血病（B - CLL）中作为生长刺激因子发挥作用。首先，重组BCGF - 12KD在检测的4例B - CLL患者的肿瘤性B细胞中诱导了剂量依赖性的DNA合成。其次，7个不同的B - CLL克隆分泌了一种类似BCGF - 12KD的产物，这解释了它们的增殖情况。一种针对BCGF - 12KD合成肽的中和单克隆抗体（mAb；Ac8）抑制了白血病B细胞的自发生长。相同的单克隆抗体阻断了由自发增殖的B - CLL细胞培养上清液诱导的正常扁桃体B淋巴细胞中的DNA合成。最后，BCGF - 12KD mRNA在新鲜分离的细胞（3例患者中的2例）以及体外增殖的B - CLL细胞（3例患者中的3例）中表达。这些发现强烈表明，BCGF - 12KD可以在体内和体外调节B - CLL细胞的生长。它们可能为这种常见的B淋巴细胞增殖性疾病的生物学特性提供重要见解。
