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

页码：107 / 113

页数：7

共 46 条

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