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Interleukin‐4 distinctively modifies responses of germinal centre‐like and activated B‐cell‐like diffuse large B‐cell lymphomas to immuno‐chemotherapy
Author(s) -
Sarosiek Kristopher A.,
Nechushtan Hovav,
Lu Xiaoqing,
Rosenblatt Joseph D.,
Lossos Izidore S.
Publication year - 2009
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2009.07851.x
Subject(s) - chemotherapy , b cell , germinal center , cancer research , medicine , diffuse large b cell lymphoma , lymphoma , biology , immunology , antibody
Summary Diffuse large B‐cell lymphomas (DLBCLs) can be classified into two subtypes: germinal‐centre B‐cell (GCB)‐like and Activated B‐cell (ABC)‐like tumours, which are associated with longer or shorter patient overall survival, respectively. In our previous studies, we have shown that, although DLBCL tumours of GCB‐like and ABC‐like subtypes express similar levels of IL4 mRNA, they exhibit distinct patterns of IL‐4‐induced intracellular signalling and different expression of IL‐4 target genes. We hypothesized that these differences may contribute to the different clinical behaviour and outcome of DLBCL subtypes. Herein, we demonstrated that IL‐4 increased the sensitivity of GCB‐like DLBCL to doxorubicin‐induced apoptosis and complement‐dependent rituximab cell killing. In contrast, IL‐4 protected ABC‐like DLBCL from the cytotoxic effects of doxorubicin and rituximab. The distinct effects of IL‐4 on doxorubicin sensitivity in GCB‐like and ABC‐like DLBCL cells may be partially attributed to the contrasting effects of the cytokine on Bcl‐2 and Bad protein levels in the DLBCL subtypes. These findings suggest that the different effects of IL‐4 on chemotherapy and immunotherapy‐induced cytotoxicity of GCB‐ and ABC‐like DLBCL could contribute to the different clinical outcomes exhibited by patients with these two subtypes of DLBCL.