Makrynikola V, Bradstock K F
Haematology Department, Westmead Hospital, New South Wales, Australia.
Leukemia. 1993 Jan;7(1):86-92.
Adhesion to bone marrow stroma is a key event in normal B lymphopoiesis, allowing exposure of B-cell progenitors to regulatory cytokines. In order to investigate whether similar processes are important in the proliferation of acute lymphoblastic leukaemia (ALL) cells of precursor-B type, the expression of various adhesion molecules was examined. By flow cytometry analysis, CD-44 and the integrins VLA-4 and VLA-5 were the most prominent. CD-44 and VLA-4 were expressed on all 18 cases of precursor-B ALL analysed, while VLA-5 was found on 15 of 18 cases. The integrin CD-11a was detected on 8 of 11 cases, while its ligand, CD-54, was present in 6/12. Other adhesion proteins such as beta 3 integrin, CD-56, CD-15, and Leu8 were not expressed to any significant extent. In view of the known binding of VLA-4 and VLA-5 to extracellular fibronectin (FN), the adhesion of leukaemic cells to FN was evaluated in a colorimetric assay. The precursor-B ALL cell lines REH and KM-3, and 7/15 cases of precursor-B ALL, showed detectable binding to FN. Binding to the other extracellular matrix proteins collagen type 1 and vitronectin was not observed, although two ALL cases showed some binding to laminin. The functional activity of the VLA-4 and VLA-5 molecules was examined using an inhibitory peptide and monoclonal antibodies. These studies indicated that ALL cells adhere to soluble fibronectin predominantly through the VLA-5 molecule (blockable with the PHM-2 antibody and a peptide containing the RGD sequence) although binding mediated by VLA-4 was also apparent in some experiments (blockable by a 40 kDa fragment containing the heparin-binding domain of FN and inhibitory antibodies). These results indicate that precursor-B ALL cells may adhere to marrow stroma through interaction of VLA-4 and VLA-5 with FN, although other mechanisms of adhesion may be important.
黏附于骨髓基质是正常B淋巴细胞生成过程中的关键事件，可使B细胞祖细胞接触调节性细胞因子。为了研究类似过程在前体B型急性淋巴细胞白血病（ALL）细胞增殖中是否重要，我们检测了各种黏附分子的表达。通过流式细胞术分析，CD-44以及整合素VLA-4和VLA-5最为显著。在所分析的18例前体B-ALL病例中，所有病例均表达CD-44和VLA-4，而18例中有15例表达VLA-5。在11例病例中的8例检测到整合素CD-11a，而其配体CD-54在12例中的6例中存在。其他黏附蛋白，如β3整合素、CD-56、CD-15和Leu8均未大量表达。鉴于已知VLA-4和VLA-5与细胞外纤连蛋白（FN）结合，我们通过比色法评估了白血病细胞与FN的黏附情况。前体B-ALL细胞系REH和KM-3，以及15例前体B-ALL病例中的7例，显示出可检测到的与FN的结合。未观察到与其他细胞外基质蛋白Ⅰ型胶原和玻连蛋白的结合，尽管有2例ALL病例显示出与层粘连蛋白的一些结合。使用抑制性肽和单克隆抗体检测了VLA-4和VLA-5分子的功能活性。这些研究表明，ALL细胞主要通过VLA-5分子（可被PHM-2抗体和含RGD序列的肽阻断）黏附于可溶性纤连蛋白，尽管在一些实验中由VLA-4介导的结合也很明显（可被含FN肝素结合域的40 kDa片段和抑制性抗体阻断）。这些结果表明，前体B-ALL细胞可能通过VLA-4和VLA-5与FN的相互作用黏附于骨髓基质，尽管其他黏附机制可能也很重要。
