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Early events of B-cell receptor signaling are not essential for the proliferation and viability of AIDS-related lymphoma

Leukemia volume 23, pages 807–810 (2009)Cite this article

We have evaluated whether targeting the Src family kinase (SFK) cascade, an early component of B-cell receptor (BCR) signaling, is an effective strategy to treat AIDS-related lymphoma (ARL). The incidence of non-Hodgkin's lymphomas (NHLs) is estimated to be between 4 and 10% in HIV+ individuals, although the frequency of at least some subsets appears to be decreasing with combination antiretroviral therapy. The incidence of Hodgkin's lymphoma (HL) is also increased in HIV-infected individuals, but it is not considered to be an AIDS-defining condition. The pathogenesis of lymphoma in the context of AIDS is complex and thought to be related to disrupted immune surveillance, chronic antigenic stimulation, genetic alterations, cytokine dysregulation and herpesvirus infection. Although HIV-related lymphomas are almost always of B-cell origin, they are morphologically diverse. Several subtypes are similar to lymphomas occurring in immunocompetent patients, whereas others preferentially develop in the context of AIDS. HIV-related lymphomas can be classified by morphology and immunophenotyping (as in the classification of World Health Organization), and/or by primary site of presentation (that is, systemic, primary central nervous system and body cavity). The World Health Orgnization classification divides ARL into Burkitt lymphomas; diffuse large B-cell lymphomas (DLBCL) that can be sometimes separated into centroblastic and immunoblastic categories; HL; primary effusion lymphomas (PELs), plasmablastic lymphomas (oral cavity or associated with multicentric Castleman's disease), polymorphic BCLs and primary central nervous system lymphomas.1 Viral associations are particularly common in ARL. Epstein–Barr virus (EBV) is present in most primary central nervous system lymphomas and AIDS-related HL, and in approximately half of the cases of DLBCL (most frequently in the immunoblastic subtype), plasmablastic lymphomas of the oral cavity and polymorphic BCLs. PELs contain the Kaposi's sarcoma herpesvirus (KSHV or human herpesvirus 8 (HHV-8)), and approximately 90% of cases are also coinfected by EBV.

Src family kinases (SFKs) are activated after ligation of the B cell receptor (BCR), and they phosphorylate downstream signaling proteins in tyrosine residues relaying B-cell signaling cascades that lead to B-cell activation and proliferation. These kinases play an important role in lymphoma pathogenesis.2 We have shown in a companion study that Src kinases are constitutively active in DLBCL cells in immunocompetent individuals, and inhibition of these kinases using dasatinib inhibits proliferation of the lymphoma cells.3 We postulated that targeting Src tyrosine kinases pharmacologically would also inhibit the survival and growth of the ARL cells.

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Acknowledgements

This study was supported by the AIDS Malignancy Consortium grant number CA-121947.

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  1. Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA

    P Lu, C Yang, I Guasparri, Y L Wang & E Cesarman

  2. The Viral Oncology Program, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA

    W Harrington

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  1. P Lu
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the AIDS Malignancy Clinical Trials Consortium

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Correspondence to Y L Wang or E Cesarman.

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Lu, P., Yang, C., Guasparri, I. et al. Early events of B-cell receptor signaling are not essential for the proliferation and viability of AIDS-related lymphoma. Leukemia 23, 807–810 (2009). https://doi.org/10.1038/leu.2008.304

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