Diagnostic Breakthrough with Burkitt Lymphoma

An international research study involving the National Cancer Institute (NCI) and 11 other institutions has successfully identified the gene expression signature for Burkitt lymphoma. The discovery, which is reported in the June 8 edition of The New England Journal of Medicine, will allow physicians to better diagnose and treat Burkitt lymphoma and better distinguish it from another more common form of malignant lymphoma.

Burkitt lymphoma is a rare aggressive B cell lymphoma that accounts for 30-50% of lymphomas in children but only 1-2% of lymphomas in adults. Burkitt lymphoma is rapidly fatal if untreated, but it is curable with intensive therapy.

The article featured the results of 2 studies on the molecular diagnosis of Burkitt lymphoma involving several European and North American institutions. One of the research teams was led by Wing (John) Chan, MD, the Amelia and Austin Vickery Professor of Pathology and co-director of the Center for Lymphoma and Leukemia Research at University of Nebraska Medical Center, and Louis Staudt, MD, PhD, head of the molecular biology of lymphoid malignancies section at the NCI. The research was supported through a multi-million dollar NCI Director Challenge Grant awarded to Chan.

"Our group studied the gene expression profiles of 71 previous, untreated HIV-negative patients with sporadic Burkitt lymphoma or Burkitt-like lymphoma," said Kai Fu, MD, PhD, assistant professor, pathology and microbiology, at UNMC and the second author of the study. "We successfully identified a gene expression signature for Burkitt lymphoma that clearly distinguishes Burkitt lymphoma from DLBCL."

Using the gene expression signature for Burkitt lymphoma, the group was readily able to distinguish Burkitt lymphoma from DLBCL by the high expression of the c-myc target gene as well as a subset of other target genes.

Overall survival was markedly superior for patients with a molecular diagnosis of Burkitt lymphoma, as they were given an intensive chemotherapy regimen instead of a lower dose regimen. Notably, 8 cases given a pathological diagnosis of DLBCL were re-classified by gene expression as Burkitt lymphoma. These cases had all the gene expression hallmarks of Burkitt lymphoma, suggesting that they represent cases of Burkitt lymphoma that are difficult to diagnose by current methods.

The study results would suggest that gene expression profiling is an accurate, quantitative method to distinguish Burkitt lymphoma from DLBCL, Fu said. "This study gives us another example of the usefulness of gene expression profiling for defining biologic entities with important implications for clinical research and practice," he said.

Burkitt lymphoma features a high degree of proliferation of the malignant cells and deregulation of the c-myc gene, which is characteristic of Burkitt lymphoma. The distinction between Burkitt lymphoma and diffuse large B cell lymphoma (DLBCL), the most common form of non-Hodgkin's lymphoma in adults, is critical, because the management of these two diseases differs. About 300 new cases of Burkitt lymphoma, typically in children, are diagnosed in the U.S. each year.

Whereas a relatively low-dose chemotherapy regimen is typically used to treat DLBCL, this regimen is inadequate for Burkitt lymphoma, which requires intensive chemotherapy. In addition, because of the high risk of central nervous system involvement with Burkitt lymphoma, it is essential that intrathecal or systemic chemotherapy that crosses the blood-brain barrier be administered. This type of chemotherapy is unnecessary in most cases of DLBCL.

In addition to Drs. Chan and Fu, other UNMC participants included: Tim Greiner, MD, and Dennis Weisenburger, MD, both professors in the department of pathology and microbiology; Bhavana Dave, PhD, associate professor, cytogenetics, Munroe-Meyer Institute; Warren Sanger, PhD, professor and discipline director, cytogenetics; Munroe-Meyer Institute; Julie Vose, MD, professor and chief of oncology-hematology; James Armitage, MD, professor, oncology-hematology; and Martin Bast, health data coordinator, oncology-hematology.