Sivaraman S, Deshpande C G, Ranganathan R, Huang X, Jajeh A, O'Brien T, Huang R W, Gregory S A, Venugopal P, Preisler H D
Rush Cancer Institute, Rush Presbyterian-St Luke's Medical Center, Chicago, Illinois 60612-3750, USA.
Microsc Res Tech. 2000 Aug 1;50(3):251-7. doi: 10.1002/1097-0029(20000801)50:3<251::AID-JEMT9>3.0.CO;2-7.
Tumor necrosis factor alpha (TNF alpha) is a pleiotropic cytokine that is constitutively produced by leukemic cells in B Chronic Lymphocytic Leukemia (B-CLL). It has been shown to have autocrine and paracrine functions in normal B cells and in B lymphoproliferative diseases. This study was conducted to determine the effect of TNF alpha (in vitro) on CD20 expression on cells from patients with B-CLL. Currently, anti-CD20 monoclonal antibody therapy is becoming a second line treatment in the management of B cell disorders like low-grade non-Hodgkin's lymphoma (NHL) and B-CLL. Our results demonstrate amply that very low doses of TNF alpha (0. 0125 ng/ml) can be used to significantly increase CD20 expression on cells from patients of B-CLL as evidenced by increases in both percentage positivity and mean fluorescence intensity. The upregulation is evident as early as 24 hours and is maintained for up to 72 hours. We propose that the upregulation is a direct result of in vitro differentiation stimulated by TNF alpha. The results presented can be exploited in the designing of priming protocols prior to antibody therapy and this is discussed.
肿瘤坏死因子α(TNFα)是一种多效性细胞因子,由B慢性淋巴细胞白血病(B-CLL)中的白血病细胞组成性产生。它已被证明在正常B细胞和B淋巴细胞增殖性疾病中具有自分泌和旁分泌功能。本研究旨在确定TNFα(体外)对B-CLL患者细胞CD20表达的影响。目前,抗CD20单克隆抗体疗法正成为治疗B细胞疾病(如低度非霍奇金淋巴瘤(NHL)和B-CLL)的二线治疗方法。我们的结果充分表明,极低剂量的TNFα(0.0125 ng/ml)可用于显著增加B-CLL患者细胞上的CD20表达,阳性百分比和平均荧光强度的增加证明了这一点。上调早在24小时就很明显,并持续长达72小时。我们认为上调是TNFα刺激体外分化的直接结果。所呈现的结果可用于在抗体治疗之前设计启动方案,并对此进行了讨论。