Douglas R S, Capocasale R J, Lamb R J, Nowell P C, Moore J S
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104-6082, USA.
Blood. 1997 Feb 1;89(3):941-7.
Chronic lymphocytic leukemia (CLL) is the most common leukemia of the western world and is characterized by a slowly progressing accumulation of clonal CD5+ B cells. Our laboratory has investigated the role of transforming growth factor-beta (TGF-beta) and interleukin-4 (IL-4) in the pathogenesis of B-cell expansion in CLL. In vitro addition of TGF-beta did not increase spontaneous apoptosis of B cells from most CLL patients, as determined using the TUNEL method, compared with a twofold increase observed in cultures of normal B cells. There was similar expression of TGF-beta type II receptors on both CLL B cells and normal B cells. In contrast to apoptosis, CLL B-cell proliferation was variably inhibited with addition of TGF-beta. In vitro addition of IL-4, previously reported to promote CLL B-cell survival, dramatically reduced spontaneous apoptosis of CLL B cells compared with normal B cells. CLL B-cell expression of IL-4 receptors was increased compared to normal B cells. Thus, our results show aberrant apoptotic responses of CLL B cells to TGF-beta and IL-4, perhaps contributing to the relative expansion of the neoplastic clone.
慢性淋巴细胞白血病（CLL）是西方世界最常见的白血病，其特征是克隆性CD5 + B细胞缓慢进展性积累。我们实验室研究了转化生长因子-β（TGF-β）和白细胞介素-4（IL-4）在CLL中B细胞扩增发病机制中的作用。与正常B细胞培养物中观察到的两倍增加相比，使用TUNEL法测定，体外添加TGF-β并未增加大多数CLL患者B细胞的自发凋亡。CLL B细胞和正常B细胞上II型TGF-β受体表达相似。与凋亡相反，添加TGF-β可不同程度地抑制CLL B细胞增殖。先前报道IL-4可促进CLL B细胞存活，体外添加IL-4与正常B细胞相比，显著降低了CLL B细胞的自发凋亡。与正常B细胞相比，CLL B细胞IL-4受体表达增加。因此，我们的结果显示CLL B细胞对TGF-β和IL-4的凋亡反应异常，这可能有助于肿瘤克隆的相对扩增。
