Therapeutic implications of Src independent calcium mobilization in diffuse large B-cell lymphoma

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• 作者：C. Annette Hollmann ; Alex ; ar Tzankov ; Veró ; nica L. Martd ; nez-Marignac ; Kristi Baker ; Czeslawa Grygorczyk ; Ryszard Grygorczyk ; William Foulkes ; Jay Nadeau ; Stephan Dirnhofer ; Raquel Aloyz
• 关键词：Dasatinib ; Lymphoma ; De novo resistance ; Calcium
• 刊名：Leukemia Research
• 出版年：2010
• 出版时间：May 2010
• 年：2010
• 卷：34
• 期：5
• 页码：585-593
• 全文大小：2472 K

文摘

We report that 38 % of primary large B-cell lymphoma (DLBCL) tested expressed active Src family kinases, which are targeted by dasatinib. The expression of active Src family of kinases (SFK) in primary DLBCL tumors correlated with unfavorable prognostic markers such as Ki67 and Mum1. Using four DLBCL cell lines we found that: (1) sensitivity to dasatinib (but not imatinib) varied 400-fold; (2) dasatinib resistance was associated with distinct signaling profiles downstream of BCR activation. In particular, although Src family kinase phosphorylation was inhibited by 100–150 nM dasatinib in all cell lines, this failed to inhibit BCR-mediated Blnk phosphorylation, calcium signaling and proliferation in a dasatinib resistant cell line.