Abstract

Non-Hodgkin's B-cell lymphoma is seen in greatly-elevated frequency in the acquired immunodeficiency syndrome (AIDS) and in infection with the human immunodeficiency virus (HIV). In this application, the Principal Investigator proposes studies to elucidate the molecular epidemiology of AIDS-lymphoma. In preliminary work, the Principal Investigator found that elevated serum levels of sCD23, as well as elevated levels of other immune system molecules (IgE, sCD27), precede the appearance of AIDS-lymphoma. Also, the elevated levels of sCD23 seen to precede AIDS-lymphoma may be due to the production of this molecule by tumor cells. In the proposed studies, the Investigator and associates will test the hypotheses that the over-expression of sCD23 (and other molecules) that precedes AIDS-lymphoma reflects: (1) immune dysfunction leading to B-cell hyper-activation and enhanced Ig isotype switching, perhaps contributing to the c-myc:Ig gene chromosomal translocation commonly seen in this cancer, or alternatively, (2) the production of these substances (sCD23 and other molecules) by the lymphoma cells themselves, or (3) reactivation of EBV infection. Also, they will examine the predictive value of the expression of these molecules for AIDS-lymphoma, and the expression of these molecules in lymphoma not associated with HIV infection, including African endemic Burkitt's lymphoma.
Their specific aims are to: (1) define the pattern of expression of sCD23 prior to the emergence of AIDS-lymphoma; (2) determine/confirm which immune system molecules, other than sCD23, are elevated in those who develop AIDS-lymphoma; (3) determine if the measurement of serum levels of molecules other than sCD23 provides additional information for predicting the appearance of AIDS-lymphoma; and (4) determine if sCD23 or other immune system molecules are elevated in non-Hodgkin's B-cell lymphoma not associated with HIV infection, or in AIDS-lymphoma in hemophiliacs. The accomplishment of these specific aims will add valuable new information to our understanding of the molecular epidemiology of AIDS-lymphoma, as well as the role of immune dysfunction in the generation and growth of this cancer.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA073475-03
Application #
2895835
Study Section
AIDS and Related Research Study Section 2 (ARRB)
Program Officer
Starks, Vaurice
Project Start
1997-09-30
Project End
2001-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Breen, Elizabeth Crabb; Hussain, Shehnaz K; Magpantay, Larry et al. (2011) B-cell stimulatory cytokines and markers of immune activation are elevated several years prior to the diagnosis of systemic AIDS-associated non-Hodgkin B-cell lymphoma. Cancer Epidemiol Biomarkers Prev 20:1303-14
Regidor, Deborah L; Detels, Roger; Breen, Elizabeth C et al. (2011) Effect of highly active antiretroviral therapy on biomarkers of B-lymphocyte activation and inflammation. AIDS 25:303-14
Epeldegui, Marta; Vendrame, Elena; Martínez-Maza, Otoniel (2010) HIV-associated immune dysfunction and viral infection: role in the pathogenesis of AIDS-related lymphoma. Immunol Res 48:72-83
Wong, Hui-Lee; Breen, Elizabeth C; Pfeiffer, Ruth M et al. (2010) Cytokine signaling pathway polymorphisms and AIDS-related non-Hodgkin lymphoma risk in the multicenter AIDS cohort study. AIDS 24:1025-33
Widney, Daniel P; Gui, Dorina; Popoviciu, Laura M et al. (2010) Expression and Function of the Chemokine, CXCL13, and Its Receptor, CXCR5, in Aids-Associated Non-Hodgkin's Lymphoma. AIDS Res Treat 2010:164586
Aissani, Brahim; Ogwaro, Kisani M; Shrestha, Sadeep et al. (2009) The major histocompatibility complex conserved extended haplotype 8.1 in AIDS-related non-Hodgkin lymphoma. J Acquir Immune Defic Syndr 52:170-9
Cozen, W; Cerhan, J R; Martinez-Maza, O et al. (2007) The effect of atopy, childhood crowding, and other immune-related factors on non-Hodgkin lymphoma risk. Cancer Causes Control 18:821-31
Epeldegui, Marta; Breen, Elizabeth Crabb; Hung, Yee Ping et al. (2007) Elevated expression of activation induced cytidine deaminase in peripheral blood mononuclear cells precedes AIDS-NHL diagnosis. AIDS 21:2265-70
Epeldegui, Marta; Hung, Yee Ping; McQuay, Amy et al. (2007) Infection of human B cells with Epstein-Barr virus results in the expression of somatic hypermutation-inducing molecules and in the accrual of oncogene mutations. Mol Immunol 44:934-42
Breen, Elizabeth Crabb; Fatahi, Sepi; Epeldegui, Marta et al. (2006) Elevated serum soluble CD30 precedes the development of AIDS-associated non-Hodgkin's B cell lymphoma. Tumour Biol 27:187-94

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