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Back to Oncology Articles
Monday 12th June, 2006
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A gene expression signature clearly distinguishes
Burkitt lymphoma from DLBCL, a critical distinction
in diagnosis.
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An international research study involving the University
of Nebraska Medical Center, the National Cancer Institute
and 10 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 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 to 50 percent of lymphomas in children but only
1 to 2 percent of lymphomas in adults. Burkitt lymphoma is
rapidly fatal if untreated, but it is curable with intensive
therapy.
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. The article in The New England Journal of Medicine featured
the results of two 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, M.D., the Amelia and Austin Vickery
Professor of Pathology and co-director of the Center for
Lymphoma and Leukemia Research at UNMC, and Louis Staudt,
M.D., Ph.D., head of the molecular biology of lymphoid
malignancies section at the National Cancer Institute. The
research was supported through a multi-million dollar
Director Challenge Grant awarded to Dr. Chan by the National
Cancer Institute.
?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,
M.D., Ph.D., 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.
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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, eight 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, Dr. 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.
In addition to Drs. Chan and Fu, other UNMC participants
included: Tim Greiner, M.D., and Dennis Weisenburger, M.D.,
both professors in the department of pathology and
microbiology; Bhavana Dave, Ph.D., associate professor,
cytogenetics, Munroe-Meyer Institute; Warren Sanger, Ph.D.,
professor and discipline director, cytogenetics;
Munroe-Meyer Institute; Julie Vose, M.D., professor and
chief of oncology-hematology; James Armitage, M.D.,
professor, oncology-hematology; and Martin Bast, health data
coordinator, oncology-hematology.
References
New England Journal of Medicine
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