Research into Non-AIDS Lymphomas

Burkitt Lymphoma and Malaria

Endemic Burkitt lymphoma (BL) has been associated with EBV and Falciparum malaria infections, but the role of these agents is poorly understood. As background for a new, cost-effective approach to clarifying these associations through the use of extant specimens, in FY2006 the Branch completed development work on three fronts. First, we found that EBV viral load was extremely high in Ugandan children with sickle cell disease; whether EBV DNA can be detected and quantified in old sera remains to be proven. Second, we determined that DNA extracted from 30-year-old Ugandan sera from the West Nile cohort study of BL are suitable for genetic polymorphism analysis. Third, we are working with the NCI Core Genotyping Facility to develop Taqman assays to determine polymorphisms in six malaria-resistance genes. If the development work succeeds, in FY2007-2008 IIB will compare the risk of BL associated with hemoglobin S and five other malaria-resistance genetic polymorphisms in DNA extracted from pathology tissue of BL cases compared to tissue of BL-free controls, adjusted for data abstracted from medical records, in Uganda. Simultaneously, the same polymorphisms and perhaps EBV load will be assessed in extant sera from BL cases and matched controls.

Oncogene Translocations and NHL

NHLs characteristically have oncogene-activating chromosomal translocations, such as the prototypic t14;18 of follicular lymphoma involving BCL2 and the CMYC activating translocation t8;14 in Burkitt lymphoma. Analyses with specimens from IIB's HIV-infected cohorts and collections from collaborators are planned. It is clear that these mutations are not sufficient to cause malignant transformation, since low level t14;18 is detectable in up to 50% of healthy individuals. IIB has proposed collaborations with several large population-based cohorts to determine whether the prevalence or level of t14;18 is associated with risk of NHL and to investigate the clonal relationship between translocation-bearing cells and subsequent tumors. If approved, this would be completed in FY2009.

HTLV-I and Adult T-cell Leukemia/Lymphoma

Field studies of adult T-cell leukemia/lymphoma (ATL) and other conditions related to HTLV-I infection in Jamaica terminate in FY2006, 23 years after they were initiated. In FY2007, analyses will be completed on host genetic variants related to ATL and other T-cell lymphomas in this Afro-Caribbean population and on predictive viral and immunologic markers of ATL in Jamaican and five other cohorts.