Engagement of alpha4beta1 integrin by fibronectin induces in vitro resistance of B chronic lymphocytic leukemia cells to fludarabine.
Engagement of alpha4beta1 integrin by fibronectin induces in vitro resistance of B chronic lymphocytic leukemia cells to fludarabine.
复制标题
纤连蛋白与 α4β1 整合素的结合可诱导 B 慢性淋巴细胞白血病细胞对氟达拉滨产生体外耐药性。
DOI：
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发表时间：
2002
影响因子：
5.5
通讯作者：
A. García
中科院分区：
文献类型：
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作者：
M. T. de la Fuente;B. Casanova;Jose V. Moyano;M. Garcı́a;L. Sanz;J. García;Augusto Silva;A. García
B细胞慢性淋巴细胞白血病的特征是体内异常的生存信号导致恶性B淋巴细胞的聚集。此前，我们发现B-CLL细胞与纤维连接蛋白片段H89(α4β1整合素的配体)的粘附性可以在体外阻止其自发凋亡。我们现在已经研究了Alpha4beta1/H89相互作用是否影响B-CLL细胞对治疗药物氟达拉滨的反应。在氟达拉滨处理期间，培养在H89上的B-CLL细胞的平均存活率(P<；0.05)显著高于培养在对照多聚赖氨酸上的细胞(P<；0.05)。在EHEB细胞系中也得到了类似的结果。经氟达拉滨处理48h后，对细胞中Bcl2家族蛋白表达的分析表明，在H89上培养的细胞中，Bclxl的表达水平显著高于在聚赖氨酸上培养的细胞(P<；0.05)，并且与H89上培养的细胞存活率呈正相关(r=0.56，P<；0.05)。这些结果表明，Bclxl参与了Alpha4beta1结扎诱导的生存信号，并可能参与了B-CLL的渐进性耐药。
B-cell chronic lymphocytic leukemia is characterized by the accumulation of malignant B lymphocytes as a result of abnormal survival signals operating in vivo. Previously, we showed that adhesion of B-CLL cells to the fibronectin fragment H89, a ligand for alpha4beta1 integrin, prevents their spontaneous apoptosis in vitro. We have now studied whether alpha4beta1/H89 interaction affected the response of B-CLL cells to the therapeutic drug fludarabine. B-CLL cells cultured on H89 during treatment with fludarabine showed significantly higher mean viability (P<0.05) than cells cultured on the control polylysine for all doses of drug tested. Similar results were obtained with the EHEB cell line. Analysis of the expression of Bcl-2-family proteins after 48 h of fludarabine treatment revealed that Bcl-xL levels were significantly higher (P<0.05) for cells cultured on H89 than on polylysine and correlated (r=0.56, P<0.05) with the increased cell viability observed on H89 cultures. These results indicate that Bcl-xL is involved in the survival signals induced by alpha4beta1 ligation and may contribute to the progressive drug resistance observed in B-CLL.