%0 Journal Article
%T Novel Therapies for Aggressive B-Cell Lymphoma
%A Kenneth A. Foon
%A Kenichi Takeshita
%A Pier L. Zinzani
%J Advances in Hematology
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/302570
%X Aggressive B-cell lymphoma (BCL) comprises a heterogeneous group of malignancies, including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, and mantle cell lymphoma (MCL). DLBCL, with its 3 subtypes, is the most common type of lymphoma. Advances in chemoimmunotherapy have substantially improved disease control. However, depending on the subtype, patients with DLBCL still exhibit substantially different survival rates. In MCL, a mature B-cell lymphoma, the addition of rituximab to conventional chemotherapy regimens has increased response rates, but not survival. Burkitt lymphoma, the most aggressive BCL, is characterized by a high proliferative index and requires more intensive chemotherapy regimens than DLBCL. Hence, there is a need for more effective therapies for all three diseases. Increased understanding of the molecular features of aggressive BCL has led to the development of a range of novel therapies, many of which target the tumor in a tailored manner and are summarized in this paper. 1. Introduction Many variations of aggressive B-cell lymphoma (BCL) exist, each with distinct molecular, biological, and cytogenetic characteristics [1]. Examples include diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, and mantle cell lymphoma (MCL). Malignant lymphomas can arise at multiple stages of normal B-cell development, with the germinal center serving as the probable origin of many types of lymphoma [2]. In the germinal-center reaction, mature B cells are activated by antigen, in conjunction with signals from T cells. During this process, B-cell DNA is modified, which results in an altered B-cell receptor. These genetic modifications are prerequisite to a normal immune response but are also the source of genetic defects that result in accumulated molecular alterations during the lymphomagenesis process [3¨C5]. DLBCL is the most common lymphoid malignancy, accounting for approximately 25 to 30% of all adult lymphomas in the western world [6]. Chemoimmunotherapy with rituximab plus anthracycline-based combination regimens has substantially improved long-term disease control, with more than 50% of patients still in remission 5 years after treatment [7¨C10]. There are 3 histologically indistinguishable molecular subtypes of DLBCL: the activated B-cell-like (ABC) subtype, the germinal-center B-cell-like (GCB) subtype, and primary mediastinal BCL (PMBL) [11¨C13]. These subtypes differ in terms of gene expression [13, 14] and are believed to originate in B cells at different stages of differentiation [15]. In addition, the process of malignant
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