Gene Expression Profiles in AIDS-Related Lymphomas (ARL): Burkitt Lymphoma (BL) and Diffuse Large B-Cell Lymphoma-Immunoblastic Variant (DLBCL-IBL)
Reviewer: Ryan Smith, MD
Last Modified: December 9, 2002
Presenter: Sven de Vos
Presenter's Affiliation: UCLA
Type of Session: Scientific
Primary CNS lymphoma and other malignant lymphomas continue to be a large problem in patients with AIDS. The most common type of lymphoma in these patients include Burkitt lymphoma (BL) and diffuse large B cell lymphoma, especially that of the immunoblastic type (DLBCL-IBL). These lymphomas that develop in the AIDS population cannot be differentiated from classical non-AIDS lymphoma of the same type by immunoserology or c-myc mutations alone. This study was done to expand on the understanding of the pathogenesis of the AIDS-related lymphomas (ARL) and to attempt to differentiate them from non-AIDS lymphomas.
Materials and Methods
- DNA samples and expression of certain genes by PCR were obtained from 10 AIDS patients with BL and DLBCL-IBL. They were compared with samples from 24 patients with non-AIDS diffuse large B cell lymphoma.
- 90% of the BL samples were taken from nodal sites of disease
- 63% of the DLBCL-IBL samples were nodal
- 40% of the BL patients were EBV positive, compared to 60% of the DLBCL-IBL patients
- No primary CNS lymphomas were included in the study
- 53 genes were identified that showed differential expression that distinguished all 3 of the lymphoma subtypes
- 83 genes were identified that classified and differentiated the ARLs (BL and DLBCL-IBL)
Examples of specific differentiating genes were given:
- c/EBP beta, which is involved in the regulation of the differentiation of mesenchymal, epithelial, and hematologic subtypes. It was expressed in 67% of AIDS related DLBCL-IBL, compared to only 13% of BL.
- TACI, a stimulator of B and T cells, was also very high in DLBCL-IBL with very little expression in BL.
- HDAC1, a corepressor in transcription factors was higher in ARL than in non-AIDS DLBCL-IBL
- ARL have distinct gene expression profiles that distinguish them from one another and from non-AIDS DLBCL-IBL.
- These data may help identify candidate genes (c/EBP beta, TACI, HDAC1) in the oncogenesis of the aggressive lymphomas.
- Further studies should concentrate on these genes to help in the definition of these genes' effects
Lymphoma is a significant cause of death in patients with AIDS. These deaths are mainly from CNS lymphoma, Burkitt's lymphoma and diffuse large B cell lympohma, especially the immunoblastic type. Classical tests, like EBV serology and evaluation for c-myc mutations have failed to differentiate ARL from non-AIDS lymphomas. Patients with ARL do worse than those with non-AIDS lymphomas, likely secondary to more aggressive disease and the fact that AIDS patients may not tolerate the aggressive therapy as well as patients that do not have AIDS. Therefore, it would be beneficial to be able to differentiate ARLs from those lymphomas occurring in non-AIDS patients so that therapies and diagnoses could possibly be tailored. This study represents a necessary first step in this differentiation, identifying several genes that are different in AIDS related BL, DLBCL-IBL, and non-AIDS diffuse large B cell lymphomas. The candidate genes identified should be further studied to attempt to differentiate the pathogenesis and disease course of ARLs.
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