Low-dose fludarabine increases rituximab cytotoxicity in B-CLL cells by triggering caspases activation in vitro

被引：13
|
作者：
Furlan, Anna [2 ]
Villanova, Federica [1 ]
Pietrogrande, Francesco [3 ]
Celadin, Marilena [4 ]
Sanzari, Mariella [4 ]
Vianello, Fabrizio [1 ,3 ]
机构：
[1] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Invest Sci, London, England
[2] Ca Foncello Hosp, Dept Internal Med, Treviso, Italy
[3] Padua Univ Hosp, Chair Med 2, Padua, Italy
[4] Padua Univ Hosp, Dept Lab Med, Padua, Italy
来源：
LEUKEMIA & LYMPHOMA | 2010年 / 51卷 / 01期
关键词：
B-CLL; apoptosis; chemotherapy; rituximab; fludarabine; caspases; CHRONIC-LYMPHOCYTIC-LEUKEMIA; LYMPHOMA-CELLS; DNA-REPAIR; APOPTOSIS; COMPLEMENT; MECHANISM; CLOFARABINE; EFFICACY; PATHWAY; DRUGS;
D O I：
10.3109/10428190903349688
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Rituximab maintenance therapy provides a significant benefit in patients with indolent B-cell non-Hodgkin lymphoma (NHL). Based on its efficacy in improving response to chemotherapy, the anti-CD20 antibody is currently under evaluation as maintenance therapy also in patients with B-CLL. We evaluated rituximab-mediated cytotoxicity in 10 B-CLL cases pretreated in vitro with non-cytotoxic concentrations of fludarabine. This combination induced a synergic cytotoxic effect in 8 out of 10 patients at a mean level of 26.15 +/- 13.9%, compared to 8.05 +/- 5.3% cytotoxicity observed with rituximab alone. Consistent with the viability assay, we found an increased caspase-3 activity together with activation of caspase-9 in B-CLL cells sensitive to sequential non-cytotoxic fludarabine and rituximab exposure. Non-cytotoxic fludarabine concentrations may sensitize B-CLL cells to rituximab-mediated cytotoxicity via caspase-3 activation.
引用
收藏
页码：107 / 113
页数：7
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